FFXIII and MW2, blech.

Sonic Support Squad ASSEMBLE!

(You should... uh... be stabbed with it! Ha!)

Quite a few...

Resident Evil 5 (RE4 is one of my favorite games ever, didn't even get this after the demo - really hate AI controlled co-op and only wanted to play it single player.)
Gears 2 (not exactly sure why, Didn't really like the more stylized art style as much as the more realistic looking original, perhaps didn't like it as much simply because it didn't give the great initial impression the original gave)
GTA IV (Cell phone and related stupid missions just killed it)
Resistance 2 (Single player definetly a step-backwords)

But the singleplayer was a drastically improved experiance and it introduced horde mode!

Still I can understand if you liked Gow MP this would be a massive dissapointment.

Monster Hunter Squad UNITE!!! 

* Realises he's alone and flees *

DMC4. The game was far shorter than it's predecessor, and playing through the same areas twice as a dumbed down character doesn't do much to make it exciting. This lack of length and content made the game boring rather swiftly.

Tales of Symphonia 2 and Resident Evil 5 are my biggest disappointments this gen. Someone screwed up

I agree, horde was more than enough to make up for a broken online system

OK, so far FFXIII & MW2 are the leaders. I've listed below, the games that have received 2 or more votes and the number of votes they received.

FFXIII 5
MW2 4
R2 3
RE5 3
Gears 2 2
FEAR 2 2
9 games have had 1 vote

Soul Calibur 4