:)

There is no reason you shouldn't use a USB audio device. It will perform as well as any other within its design limits. I have a USB audio mixer with 16 in 2 out and I have had no problems using it. It is USB 2 and that is the most common USB support.  

I used and still occasionally do a MOTU 24io which operates off of it's own pci card. Recently, I switched to a pair of Roland Studio Captures run in sync, both of which are USB. With X3 and the studio captures I am getting lower latency than the dedicated pci card! Now, I have not been able to wring the system out on 32 tracks live yet. But the results working in the studio so far have been phenomenal!

I was in the same exact position just a couple of weeks ago having to choose between the  Saffire Pro 40 or Scarlette 18i20. I chose the Saffire and stayed with Firewire simply because I had exceptional performance with it. I wasn't sure if I'd get the same level of performance from USB. One thing I can say is the Saffire Pro 40 is an amazing piece of hardware for its price point. I absolutely love the thing and it is Thunderbolt ready so if I ever need to upgrade in the future I will be able to do so.  Good luck with your decision.

Interesting timing for this question. I just bought a firewire cable to test my RME UCX to see if the round trip is shorter with Firewire.
 
The results...
Firewire
69 samples input
126 samples output.
195 samples round trip
 
USB
76 input
93 output
169 round trip
 
So for my interface, running with a 48 sample buffer, I get a faster round trip with USB.
 
There is the benefit of Firewire that I don't have to plug in the interface.
 
 

I have been working with a MOTU series 828 from the Mk II to the Mk III to the Mk III Hybrid and have found the Firewire 6 pin standard (Firewire 400) to be superior to USB 2.0 - because of the DUPLEX nature of packet handling, and possilby the fact that MOTU has to convert the USB protocol.  Before I post the transfer speeds of the relative technologies, it is important to note that it is not the speed, but the packet processing communications protocol employed which is important.  Namely whether or not the standard uses DUPLEX communications as opposed to HALF-DUPLEX communications.  In half-duplex, only one transmitter may speak at a time, so it is like a single tunnel through which trains must pass while traveling in opposite directions.  One train must wait for the oncoming train to clear the tunnel before it can enter and continue - so that fact that the train travels 30 mph or 35 mph through the tunnel is of little consequence - if it still spent most of its delay time in the waiting queue.  So Duplex protocols mean that travel can happen in both directions at the same time, which is THE biggest deal, much more important than transmission speed.
 
The key is not transmission speed, rather the following in my best, experience.  This is why - my MOTU picked up in performance when I switched from USB 2.0 to a PCI-e Firewire 400 card.  The extra 80 Mbps in the USB 2.0 was rendered moot by its half-duplex protocol.  Ideally then, USB 3.0 is the best of all worlds, provided the chipset compatibility issue is negated.
 
Level of Importance
1.  DUPLEX communications over HALF-DUPLEX

1. USB 3.0  -  DUPLEX
2. Firewire 800 – DUPLEX
3. USB 2.0 – HALF-DUPLEX
4. FireWire 400 – DUPLEX
5. USB 1.1 – HALF-DUPLEX

2.  Chipset compatibility
      TI or VIA Chipset 2012 and beyond - replace older resident sets with PCI-e expansion card
 
3.  Transmission Speed

1. USB 3.0  - 5000 Mbps (or 4 GB/sec)
2. Firewire 800 – 800 Mbps (or 75MB/sec)
3. USB 2.0 – 480Mbps (or 60MB/sec)
4. FireWire 400 – 400Mbps (or 50MB/sec)
5. USB 1.1 – 12Mbps (or 1.5MB/sec)

This is ALL very valuable input. Thanks to you all. Hahaha....now you're making my decision harder again. UGH!!!!!

I posted the question on the RME forum, curious how they would answer.
 
http://www.rme-audio.de/forum/viewtopic.php?pid=91631#p91631
 
 

I own the VS-20 and a Focusrite saffire and I love the sound and warmth of the focusrite soundcards, the award winning pres sounds like no other IMO.
 

IMO the wild variances and lack of standards in Firewire chips and interfaces is enough reason to stay away from FW interfaces if you are buying something new. Works on your computer now...might not work on the next one, etc. Its future is murky as well.
 
USB 2.0 is standardized, reliable, and plenty fast enough for most recording needs. Very high simultaneous track counts at low latencies is where USB 3.0 and other formats like Thunderbolt show promise. I've been using USB interfaces for years now after using PCIe and FW and don't see any down side personally. You must however makes sure you get a product with a solid, low-latency USB driver as it will make or break your experience.