Left 4 Dead (2) on expert. Hunters / jockeys suddenly decide that they can slap you down 20 hp whilst stunned by a shove and the damage increase on jockey's is disproportional to the difficulty, they become stronger than hunters -_-. That, and chargers somehow gain an instant recharge on their charge if they kill someone whilst charging meaning that they can wipe a group far too easily. It's nothing like what you can do on versus
Starcraft 1's AI on custom maps must have been spawning resources since it made things far too quickly and was straight unfair as terran. At least they got a little retarded when they needed an expansion
Gears of War 2 on insane (excl campaign). Bots somehow manage to perfectly no scope headshot the second after sprinting with the sniper
The fact that almost all RTS's have AI's that just know where you are and where you have expanded to without any form of recon whatsoever
At least all of the above are dealable though, generally a bit irritating but nothing too bad. Can't think of any more
Oh wait, solitaire on the iPod mini. There was always a point where you could move 2 cards to 1 location (i.e. a 7 of spades and clubs are available on 2 different collums with a 8 of hearts on another collum), one of which led to the end game and the other guaranteed a loss and the AI seemed to love to make the latter occur for whichever one I picked -_-