I remember a video on youtube a while back of someone playing an FPS (maybe Halo 2?) with the guitar hero controller. Pretty funny.
Makes me wonder if a super controller would be made where you are basically holding 2 controllers, 5 buttons each, 1 button for each finger. It would take some getting used to but imagine if 1 thumb did run, the other block, 4 fingers on one hand did the directions, and the 4 fingers on the other did attacks.
At first it'd be practically unplayable, but if you got used to it, there wouldn't be much that would be better than it. Maybe make the block button on the same hand as the directions and have the block button be a very sensitive click stick so you can press it easily to do block but if you wanted to do 360s or half circles you could use the stick for that.