Prototype 2: No Co-op. After the first game revealed to have Co-op, then they cut it, then the game got delayed for an additional 6 months, then they said that it wasn't to add Co-op, but they then promised it would be in the sequel. WTF?
Force Unleashed: I couldn't move while force grabbing people. Psi-Ops did this shit years ago, where's my spiritual or direct sequel at?!
DKCR: The waggle. The fact that it could clearly be a button, but they decided to make it waggle instead.
NiGHTS Journey of Dreams: All of its flaws would have been forgiven if they had just had a Soft Museum type level. That whole game lacked the "trippy" that the original had. Hopefully one day we'll get a true successor.
Infinite Space: The awkward combat mechanic. So much of the rest of the game seemed really appealing, but those early "dogfights" just felt like complete "dogshit."
Elder Scrolls: Oblivion: This one aspect is actually pretty major. Cyrodiil is supposed to be a dense, canopy covered, jungle infused kingdom. Think the Amazon as if it was the capital city of the continent. Why they chose to "retcon" the scenery to generic green hills and apple trees is beyond me.
Recent Sonic Games: Whatever the fucking gimmick is, whether it is a werehog, giant sword, or a human companion, they all turn me off from actually giving the game a chance.
LittleBigPlanet: the fucking jump physics. If you're going to make a platformer, the actual platforming in the game has to feel good.
Pikmin: The time limit. Proven by the fact that Pikmin 2 had no time limit and it INSTANTLY became one of my all-time favorite games.
Mario Galaxy(ies): The lame levels where for some reason I'm in a bubble and can't hit the edges. If I wanted to play a game like Kurururin, I would play that Annoying Spinning Stick game.
Prince of Persia (xbox): The first fucking boss. Is he even beatable? I guess I'll never know because I can't be bothered.
Witcher 2: The fucking combat. How did that get through playtesting? Early on it's nothing but restart, restart, restart as the player struggles to just survive 5 enemies.
Ninja Gaiden: The warehouse with the flying robots. I killed them wave after wave, but it never ended and I couldn't platform. My friend swears that eventually they stop spawning, but for me it seemed never ending. Stopped playing after that.
Animal Crossing City Folk: The grass wearing away. Actually, the fact that they fucked up the color schemes of the palettes that had otherwise stayed consistent with each iteration, meaning I couldn't "import" my old designs, completely ruined the main thing I play the series for.
Ico: The shadow people. The stress they caused ruined any of the fun I could have had trying to solve the puzzles. Towards the end of the game, it gets better because you can ditch the stick, but dear GOD.
And just for fun
Gears of War 2: it is almost too good. [/spoiler] I haven't even beaten GoW1, let alone played any of the rest.[/spoiler]