I've heard nothing but questionable stuff about Focusrite experiences - it seems to be all over the board (which is enough for me to say "no thanks"). I've had a couple of different M-Audio stuff. Their firewire line never played nice with my systems. Their USB stuff was OK, but latency was never that great, and their driver support has always been spotty. Not sure if they've improved over the years. I had one MOTU interface and sold it just a few short months later, because at the time it required very specific firewire chipsets to behave well, and I guess my system didn't cut it.
RME is legendary when it comes to driver stability, hardware performance, and support. Even their oldest hardware gets driver updates for the latest versions of Mac and Windows, which is absolutely amazing. Their components are top notch, but most of all - the driver performance (especially over USB) is unrivaled. I'm not being hyperbolic when I say that RME is truly the best of the best. There are countless threads at KVR and Gearslutz lamenting how awesome they are.
I didn't believe it 100% until I picked up my Babyface Pro. After I got it, I decided that I will never own another audio interface from another manufacturer within the first few weeks of using it. Simply put: it's THAT good.
But I digress... Might as well get 64 GB of RAM and call it a day.