South Park: Stick of Truth...As a fan of the show, I felt the game was extremely well done. Played as three different character set-ups on separate play-thrus.

Back when arcades were still popular in the 90's I used to play Street Fighter II all the time. As for recent games, I think the game that I've played the most is The Elder Scrolls V: Skyrim.

Resident Evil 4.
Played through it 12 times to date.

Mega Man X, over 50 times easily.

I've completed Fire Emblem: Path of Radiance 6 or 7 times. Can't remember how many, I just know I was close to unlocking Petrine as a Trial character.

No idea how people have the patience to unlock Ashnard.

After that would probably be Ocarina of Time or Tales of Symphonia, at 4 playthroughs. But that's excluding remakes.

FFX for long games,

Halo 2 for short games.

Super Metroid I think. Finally finished it for the first time last year, after that I've finished it over 30 more times. My record keeps getting better, a few weeks ago the end time counter showed 1:30 :) Amazing replay value.

I may have finished Spyro the Dragon (ps1)/Spyro 2 more, but that's a long time ago so I am not sure.

How can I forget about Mega Man series? And so many SNES games...

Duck hunt (NES), Exetbike (NES), Cadillacs and Dinosaurs (Aracde), Stronghold (2001), DX Ball 2, Mafia 1, GTA 3, VC and San Andreas.

That's a good question :D

I think Skyward Sword like 4 times, and I'm going for 2 more times (6 heart run, and lastly the 6 heart, shieldless, hero mode). But since I got my Wii U, I haven't played my Wii games as much.

There's also GTA: San Andreas, either 3 or 4 times; and DBZ: Budokai Tenkaichi 2, maybe 3 times.