No problem. I used a small x4 riser in order to run two double slot GFX cards in the x16 slots, allowing me to mount my Apricorn Velocity x2 card in the HD Bay 4 area and keep my USB 3.0 card installed.
I've seen people go external like you're intending, on the Xserve systems I think, but it's not something I've done. I imagine you'll want to make sure you mitigate the risk of possible ESD damage for any exposed parts. Good luck, post a pic when you're done!