Hey guys!
 
I've got a 2i4 1st Gen from Focusrite, love it been using it on my HP laptop, works like a charm. Just got a custom built monster PC and was anxious to use it with Sonar Platinum but all audio that comes through the USB interface is crackly, poppy, blendy, and even slowed at times. I reached out to Focusrite and was unable to find a solution. Disabled fast boot, the USB power savers, power management and updated the BIOS to no avail. 
 
My specs ASUS
Intel Core i7-6700K @ 4.00GHz
32 GB RAM
Realtek High Def Audio
GTX 1070
 
My DPC Latency Test:
_________________________________________________________________________________________________________
CONCLUSION
_________________________________________________________________________________________________________
Your system seems to be having difficulty handling real-time audio and other tasks. You may experience drop outs, clicks or pops due to buffer underruns. One or more DPC routines that belong to a driver running in your system appear to be executing for too long. One problem may be related to power management, disable CPU throttling settings in Control Panel and BIOS setup. Check for BIOS updates.
LatencyMon has been analyzing your system for 0:06:20 (h:mm:ss) on all processors.

_________________________________________________________________________________________________________
SYSTEM INFORMATION
_________________________________________________________________________________________________________
Computer name: DESKTOP-2CNQ6D3
OS version: Windows 10 , 10.0, build: 17134 (x64)
Hardware: ASUSTeK COMPUTER INC., Z170-AR
CPU: GenuineIntel Intel(R) Core(TM) i7-6700K CPU @ 4.00GHz
Logical processors: 8
Processor groups: 1
RAM: 32706 MB total

_________________________________________________________________________________________________________
CPU SPEED
_________________________________________________________________________________________________________
Reported CPU speed: 4008 MHz
Note: reported execution times may be calculated based on a fixed reported CPU speed. Disable variable speed settings like Intel Speed Step and AMD Cool N Quiet in the BIOS setup for more accurate results.
WARNING: the CPU speed that was measured is only a fraction of the CPU speed reported. Your CPUs may be throttled back due to variable speed settings and thermal issues. It is suggested that you run a utility which reports your actual CPU frequency and temperature.
 
_________________________________________________________________________________________________________
MEASURED INTERRUPT TO USER PROCESS LATENCIES
_________________________________________________________________________________________________________
The interrupt to process latency reflects the measured interval that a usermode process needed to respond to a hardware request from the moment the interrupt service routine started execution. This includes the scheduling and execution of a DPC routine, the signaling of an event and the waking up of a usermode thread from an idle wait state in response to that event.
Highest measured interrupt to process latency (µs): 649.709164
Average measured interrupt to process latency (µs): 2.397719
Highest measured interrupt to DPC latency (µs): 647.409761
Average measured interrupt to DPC latency (µs): 0.960707

_________________________________________________________________________________________________________
REPORTED ISRs
_________________________________________________________________________________________________________
Interrupt service routines are routines installed by the OS and device drivers that execute in response to a hardware interrupt signal.
Highest ISR routine execution time (µs): 434.452844
Driver with highest ISR routine execution time: dxgkrnl.sys - DirectX Graphics Kernel, Microsoft Corporation
Highest reported total ISR routine time (%): 0.035395
Driver with highest ISR total time: dxgkrnl.sys - DirectX Graphics Kernel, Microsoft Corporation
Total time spent in ISRs (%) 0.057721
ISR count (execution time <250 µs): 261627
ISR count (execution time 250-500 µs): 0
ISR count (execution time 500-999 µs): 7
ISR count (execution time 1000-1999 µs): 0
ISR count (execution time 2000-3999 µs): 0
ISR count (execution time >=4000 µs): 0

_________________________________________________________________________________________________________
REPORTED DPCs
_________________________________________________________________________________________________________
DPC routines are part of the interrupt servicing dispatch mechanism and disable the possibility for a process to utilize the CPU while it is interrupted until the DPC has finished execution.
Highest DPC routine execution time (µs): 1827.371507
Driver with highest DPC routine execution time: Wdf01000.sys - Kernel Mode Driver Framework Runtime, Microsoft Corporation
Highest reported total DPC routine time (%): 0.125322
Driver with highest DPC total execution time: Wdf01000.sys - Kernel Mode Driver Framework Runtime, Microsoft Corporation
Total time spent in DPCs (%) 0.172886
DPC count (execution time <250 µs): 987835
DPC count (execution time 250-500 µs): 0
DPC count (execution time 500-999 µs): 1450
DPC count (execution time 1000-1999 µs): 1
DPC count (execution time 2000-3999 µs): 0
DPC count (execution time >=4000 µs): 0

_________________________________________________________________________________________________________
REPORTED HARD PAGEFAULTS
_________________________________________________________________________________________________________
Hard pagefaults are events that get triggered by making use of virtual memory that is not resident in RAM but backed by a memory mapped file on disk. The process of resolving the hard pagefault requires reading in the memory from disk while the process is interrupted and blocked from execution.
NOTE: some processes were hit by hard pagefaults. If these were programs producing audio, they are likely to interrupt the audio stream resulting in dropouts, clicks and pops. Check the Processes tab to see which programs were hit.
Process with highest pagefault count: explorer.exe
Total number of hard pagefaults 354
Hard pagefault count of hardest hit process: 110
Number of processes hit: 19

_________________________________________________________________________________________________________
PER CPU DATA
_________________________________________________________________________________________________________
CPU 0 Interrupt cycle time (s): 11.066701
CPU 0 ISR highest execution time (µs): 353.273204
CPU 0 ISR total execution time (s): 1.660805
CPU 0 ISR count: 256983
CPU 0 DPC highest execution time (µs): 1827.371507
CPU 0 DPC total execution time (s): 5.177946
CPU 0 DPC count: 970207
_________________________________________________________________________________________________________
CPU 1 Interrupt cycle time (s): 1.257480
CPU 1 ISR highest execution time (µs): 434.452844
CPU 1 ISR total execution time (s): 0.094937
CPU 1 ISR count: 4627
CPU 1 DPC highest execution time (µs): 507.508982
CPU 1 DPC total execution time (s): 0.047922
CPU 1 DPC count: 5156
_________________________________________________________________________________________________________
CPU 2 Interrupt cycle time (s): 0.740061
CPU 2 ISR highest execution time (µs): 143.020459
CPU 2 ISR total execution time (s): 0.000841
CPU 2 ISR count: 24
CPU 2 DPC highest execution time (µs): 57.615519
CPU 2 DPC total execution time (s): 0.023433
CPU 2 DPC count: 10082
_________________________________________________________________________________________________________
CPU 3 Interrupt cycle time (s): 0.744725
CPU 3 ISR highest execution time (µs): 0.0
CPU 3 ISR total execution time (s): 0.0
CPU 3 ISR count: 0
CPU 3 DPC highest execution time (µs): 37.918663
CPU 3 DPC total execution time (s): 0.001068
CPU 3 DPC count: 402
_________________________________________________________________________________________________________
CPU 4 Interrupt cycle time (s): 0.744677
CPU 4 ISR highest execution time (µs): 0.0
CPU 4 ISR total execution time (s): 0.0
CPU 4 ISR count: 0
CPU 4 DPC highest execution time (µs): 28.505988
CPU 4 DPC total execution time (s): 0.003752
CPU 4 DPC count: 1163
_________________________________________________________________________________________________________
CPU 5 Interrupt cycle time (s): 0.737013
CPU 5 ISR highest execution time (µs): 0.0
CPU 5 ISR total execution time (s): 0.0
CPU 5 ISR count: 0
CPU 5 DPC highest execution time (µs): 29.263224
CPU 5 DPC total execution time (s): 0.002038
CPU 5 DPC count: 689
_________________________________________________________________________________________________________
CPU 6 Interrupt cycle time (s): 0.769074
CPU 6 ISR highest execution time (µs): 0.0
CPU 6 ISR total execution time (s): 0.0
CPU 6 ISR count: 0
CPU 6 DPC highest execution time (µs): 24.442365
CPU 6 DPC total execution time (s): 0.003760
CPU 6 DPC count: 1183
_________________________________________________________________________________________________________
CPU 7 Interrupt cycle time (s): 0.710221
CPU 7 ISR highest execution time (µs): 0.0
CPU 7 ISR total execution time (s): 0.0
CPU 7 ISR count: 0
CPU 7 DPC highest execution time (µs): 41.541168
CPU 7 DPC total execution time (s): 0.001441
CPU 7 DPC count: 404
_________________________________________________________________________________________________________
 
 
 
 
Would LOVE some help with this. Been banging my head at it for a week.
 
-Cable

Just curious why you have the Realtek audio listed.  I would disable that device and use the Focusrite exclusively for all audio on that PC.
 
All of your other system specs look good.  I would check that you have set your Windows power options to 100% min/max for CPU.  I also disable SpeedStep in the BIOS. https://en.wikipedia.org/wiki/SpeedStep
 
Just to be safe, also disable your network adapter and run the latency test again.

@abacab I listed Realtek as it was the default sound driver on the PC. I disabled speedstep and had already disabled the network drivers. As for performance, all the settings are set for maximum. It's strange, I can't seem to pin the tail on this.

What buffer size are you running. Both in Windows (sounds, recording, (interface)properties.)
And what drivers are you using for the focusrite?

I'm running 256, sample rate is 44.1 same as windows. Does windows have a buffer size? As for drivers, the standard Focusrite 2i4 one found here: https://us.focusrite.com/downloads?product=Scarlett+2i4+first+gen
 
No ASIO4All here

Are you getting crackling during playback or when you're trying to monitor your input in a DAW? what about just normal Windows sounds like YouTube or whatever?

It's for everything: Playback, DAW, YouTube, video games. Everything has the snap-crackle-pop® sounds 

I would disregard the Focusrite for now, since its happening with just the PC and its ops.  
I would also temporarily remove the video card and just use the CPU video for the time being.  
 
Is this a factory built PC (e.g. a Dell, ASUS, etc) or was this a custom built? 
From what spec's you list its nearly identical to mine (see my sig) and I have no problems.  I only use the Intel CPU graphics, no added card, and its more than adequate for DAW operation (and general PC ops).   However I built my own and have it very "vanilla" with no ASUS tuning programs, unneeded apps, etc.   I had a problem with a previous PC and Google Chrome installation (removing Chrome and the google updater fixed it).  I also only use the built in Windows Defender antivirus as some 3rd party AV's are known to cause problems.  
 
Finally, pops/crackles/skipping, etc is an often complaint on computer forums although not as often in Win 10.  Sadly, no "one fix" for the problem, each one has to be addressed individually.
 
One option, as I mention below, is to wipe the drive, only install Win 10, needed drivers and the DAW software and in your case the Focusrite drivers.  I see reports of users doing this with a new PC on recording forums.
 
Related, I purchased a Dell Inspiron 15 "gaming" laptop last year to use for off-site (on site) recordings.  I could never get the DPC latency acceptable and had some dropouts.  After much "tweaking" and "tuning" I finally gave up and returned the OS drive (an M.2 SSD) back to the original Dell image and installed a second SSD and only installed Windows 10, needed drivers, Sonar and Studio One 3 and the drivers for my MOTU 896Mk3 Hybrid.  Nothing else.  The laptop runs clean with Resplendence Latency Mon and also runs without any problems using Sonar (I've done several long on-site recordings and no problems).  I don't do any Sonar processing with the PC, only the recordings and the projects are transferred to my DAW desktop for any processing/mixing/mastering.  
 
 

I just ran a clean LatencyMon report on my system, and compared the resulting numbers with yours.
 
I noticed that your ISR's show a high execution time with your DirectX Graphics Kernel.  My ISR score for that driver is "0". 
 
Your CPU 0 ISR counts and total execution look a bit high also.
 
I am running Intel HD graphics on my CPU, so no discrete GPU or 3rd party graphics drivers here.  The only drivers where I got any ISR peg counts are 'Kernel Mode Driver Framework' and 'USB1.1 & 2.0 Port Driver'.
 
I think that your GTX 1070 (and the drivers) is probably worth removing as a test.  As Fireberd already suggested, try just running with the CPU integrated graphics.

This is a custom built PC, no integrated graphics just the 1070. I forgot to mention that the only hard drive is a samsung 850 evo 500GB SSD, idk if that is a problem. The drive wipe/reinstall of windows sounds like the only viable option at this point, unless there is something else ya'll suggest I try?