I'm returning to Sonar after some time away.  Part of that return included a computer upgrade (i7 multi, etc.), but I stuck with my MOTU 424/2408 interface. 
 
My setup handles 128 samples handily, but balks at 64 samples without tuning.  (clicks and pops)
 
I apologize if my question is too vague, but what would you look at first if you wanted to take the next step down. 
 
At 64 samples, but CPU isn't red-lining, but something is standing in the way.  The 424 is a PCIe.
 
18 samples is usable, but we alsways want better if possible - right?

I record with a Sample Rate of 48 k, and an ASIO Buffer Size of 128 for my audio interface, and this gives me a Sonar reported Total Round trip Latency of about 9.7 ms, or just about 5 ms one way.  This is a VERY comfortable setup for me, as it just all works without any latency issues or any CPU/processing issues.
 
If I instead change the ASIO Buffer Size to 64, then I can start out fine, but eventually the project complexity/load get to where I starting getting audio issues.  Because of this, I always run when recording, at 48 k and 128, and a record bit-depth at 24 bits.
 
Bob Bone
 

Run latencymon or one of the other latency analysis tools and it will give you some indication of what processes are causing latency.
 
One thing to check first - is WIFI adapter off?

schwa
I'm returning to Sonar after some time away.  Part of that return included a computer upgrade (i7 multi, etc.), but I stuck with my MOTU 424/2408 interface. 
 
My setup handles 128 samples handily, but balks at 64 samples without tuning.  (clicks and pops)
 
I apologize if my question is too vague, but what would you look at first if you wanted to take the next step down. 
 
At 64 samples, but CPU isn't red-lining, but something is standing in the way.  The 424 is a PCIe.
 
18 samples is usable, but we alsways want better if possible - right?

The MOTU PCIe 424 is one of the best performing audio interfaces (when it comes to super low round-trip latency).
You can't do better with any other audio interface...
 
If you have a bottle-neck in low-latency performance, it's the speed/thru-put of your computer.
You want a machine that can sustain heavy loads without any hiccups in data-flow.

schwa
I apologize if my question is too vague, but what would you look at first if you wanted to take the next step down. 
 

Do you have c1e and cool and quite disabled in the bios? I don't have those options on my HP laptop - I don't know if HP makes them available on their desktops. Is power management setup correctly? There are utilities you can run that show the processor frequency so you can check and see if the cpu is being throttled back like the intel Power Gadget. 

The suggestion of downloading and running the free Resplendence Latency Mon should be followed. 
http://www.resplendence.com/latencymon
 

I would suggest giving more system specs. 

I tried to spec a pretty high end system without building myself.
CPU is i7-5820k @3.3GHz.
32 GB RAM
System drive is an M.2 SSD.
Video is a GTX970
 
Are there any other relevant specs I should mention?

Latencymon showed the Microsoft Defender real time scanner to be a problem.  Turning that off seems to have helped, I'm able to run several projects at 64 samples.  In fact, the CPU seems so laid back, I'm temped to try 32. 
 
Is anyone running 32 samples with any success?

schwa
Latencymon showed the Microsoft Defender real time scanner to be a problem.  Turning that off seems to have helped, I'm able to run several projects at 64 samples.  In fact, the CPU seems so laid back, I'm temped to try 32. 
 
Is anyone running 32 samples with any success?

 You can modify where it scans. Usually the big hit is when it scans itself.