At first you do get sore, but then you get used to playing on the 3DS. I'll wait until the Circle Pad Pro comes out with Resident Evil: Revelations.
I like it. It sure is a lot easier to play with it. The L and R buttons are so much more accessible. Heck, I like using it for everything else too. Only drawback is that the volume control is covered and can't remove the game cartridge. I think it would be great for a tripod mount though for taking pictures, with some modification of course.
I looked at that Resident Evil game today. You getting it? I'm curious because you can do 2 player co-op and I'm not gonna get it unless I got someone to kill zombies with