I have not yet played Bioshock 2, but have been primarily playing AC2 and ME2. The main issue is you just lose that ability to quickly aim -- the twitch factor as someone else mentioned. It comes back after a day or so (from other times I've taken a break), but it really is pretty stunning how noticeable the drop off is for me.divisionbyzorro said:The dropoff depends upon what you're playing. I didn't feel much of a dropoff after playing a bunch of ME2 since the game is so different. But playing Bioshock 2 could definitely futz with your muscle memory.