I have Cerebral Palsy, and am thus confined to a wheelchair and only have use of my right arm. Right now, I'm playing Ninja Gaiden 2, one-handed. I know it sounds rather ludicrous because the NG franchise is infamous for its unforgiving difficulty, but I like the challenge. After all, I did beat NG: Black and NGDS.
My progress in NG2 has admittedly been slow (Chapter 6 on Acolyte in 2 weeks), but I think I'm doing good considering the franchise's difficulty.
Since I started playing, I've gotten some rather strange looks from the 360 community, saying
like I won't beat the game, one-handed. But, here I am, chapter 6 and still going strong.
So far, my only real problem has been the first Genshin fight (Chapter 2), because I can't block (Block is only mappable to the triggers). That's my only problem with the 360, other than the D-Pad -- the triggers and bumpers.