Here's what I'm up to:
I use an Antelope Orion32 for the 'heavy lifting' via USB. But I also use a MOTU 828 mkii for CV Tools via Firewire 400. You just have to set up the routings for these properly in whatever software your machine uses for audio multitrack routing.
But yeah, you can run multiple interfaces PROVIDED your DAW and audio routing software can deal with this properly. With Ableton, the DAW certainly doesn't have a problem with that. This is actually a bit similar to the issues one sees when adding an ADAT Lightpipe interface to another interface, then letting the machine know about the new/extra channels. And in fact, depending on what DAW interface you're using, that strategy might be the right one here; you could use one of Expert Sleepers' Lightpipe-equipped modules for that.