Deus Ex 2: Invisible War. (Main answer, here)
So, the original Deus Ex was my favourite game of all time (until about a month ago when I played The Walking Dead.)
Then I played the second Deus Ex.
Then I refused to call it a sequel to Deus Ex.
I don't even know what's up with this game. It's as though they purposefully took out everything that made the first one good, turned the bad stuff up to eleven and made the game close to windows every time you loaded an area (an actual step of the loading proccess). Only plus it had was the graphics weren't quite as bad.
The other major one is Skyrim. I really loved Daggerfall, Morrowind and Oblivion (I'm probably going to get shot for liking that last one), but Skyrim was just meh for me. I can't quite put my finger down on why, but the world just didn't feel as well realized and I really, really don't like the way levelling works. If it had been Oblivion's system with a few skills taken out and none of that level-scaling nonsense I would've enjoyed it way more, I feel. It's by no mean bad, it's just an OK game in a series where every previous installment (Except the very first one. Screw Arena) had blown my mind.
Mass Effect 2, but not because I don't like the two later Mass Effects (In fact, I liked that series more as the number on the end increased. Sue me.), but because ME1 was a Space Opera, ME2 was a space action blockbuster. A damn good one, but more games like ME1 need to exist, and we have more than enough games like ME2.
CoD: Modern Warfare 2. I hoped the sequel to the only interesting one would also be interesting. Nope.
I don't know if you can call it a sequel, but I'm going to: The Old Republic. I want KotOR 3, damnit!