Mass Effect is the only contender that is still out, and all signs point to it being. . .well, I don't have much faith in Bioware these days.
In no order:
Super Mario Galaxy - Even if the game goes totally tits up from the point I'm at on to its conclusion, it has still so far provided the best 3d platforming ever, and possibly the best platforming since Yoshi's Island. NINTENDO REDEEMED. SPACE JUNK GALAXY OMG MY THROBBING COCKUS!
Heavenly Sword - Ninja Theory's first noteworthy game is flawed and short, but it's an experience with exceptional presentation and a different take on combat. It's easy and fairly approachable, too (if you ignore the shitty demo).
Dynasty Warriors Gundam - Musou for the masses. A slightly different take on Musou with a slightly simplified formula. Also, it is basically animu porn. Whether you prefer scripted mission Musou, or more free for all, unscripted missions, this has got your boner licked.
Puzzle Quest - Oh yeah, I'm going there. The 360 version is the best, but the PSP and DS versions are no slouches either. The last quarter or so of the game drags on a bit too long, but what with it being a puzzle game, you could chip at it.
Blue Dragon - It's basically the best bits of old school JRPGs dressed up with super pretty graphics. The story, at times, is reminiscent of both Final Fantasy 4 and Dragon Quest 7. The combat system is basically FF5's. And Nobuo Uematsu proves that he just wasn't trying very hard on those last couple FF scores he did. Best JRPG in a long ass time. You can tell what gender every character is upon looking at them, a first for Japanese videogames.
Things that didn't make the cut.
Bioshock - I think you did just about everything right, but I just didn't enjoy you as much as I felt like I should. No offense! RIP Irrational.
COD4 - Honestly, I haven't played the full game. I will, but I think I might be. . .gasp. . .FPSed out. I am basically in this for multiplayer.
Halo 3 - Another game I haven't really cracked open. I will get to it when things slow down. Again, I think for the first time ever I might be FPSed out.