Yeah, unless you're left handed or missing some fingers, I don't get how WASD could be uncomfortable. For FPS or even 3rd person games like Mass Effect it's always felt perfectly natural. Of course, this coming from someone who grew up using AZOP on one of these things
I should note though, I do have an Xbox369 for Windows controller and to prefer to use it with games like Tomb Raider, Super Meat Boy and even Skyrim. It really depends on how the game is set up.