Uncharted Drakes Fortune I beat it 9 times before trophies were released, and then 3 more since. I plan on going through at least once more once it is one PS Now, and will probably do it again if they release a PS4 remaster.

As a kid I played through the Star Wars game on SNES at last 50 times. This was a great example of how a game only needs to be a couple of hours long, as long as it is a solid two hour experience.

Pokemon Emerald like 20 times!
Yeah... I really loved that game :P

Probably Phoenix Wright.

Timesplitters 2

I almost never play through games twice anymore, because there are always too many new games to play

Sonic Adventure, I completed it at least 5 times.

The Last of Us. The game's only been out a year and I'm on my fifth playthrough. What a sublime game!

Halo 3

Atari2600 and NES games have the most replay ability, followed by the 16 bit era. Anything modern? Not so much.

Metal Gear Solid Peace Walker.

I must have played through the original super mario bros a ton if you count using warps. I've got a feeling a beat Psycho Fox on the mastersystem a shocking number of times. As a kid I somehow got to the point where I thought playing through that game was easy!!!

Basically, as a kid, I use to play a handful of platformers, which lacked the ability to save, through to completion over and over and over.

For me my most completed game by far is Super Mario Bros 2. I know I've defeated the final boss many times on the nes alone. Add other versions such as Mario all stars, Super Mario Advance, vc and emulator on pc and phone I've done some serious playtime. That said, I bet I've only completed it about twice without using at least one warp. I often play with the intent not to use a warp but find myself caving into temptation when I come across one.

It's my most played game ever clocking in many many many times more play time than the critically far more loved (though vastly inferior IMHO) smb3.
I last completed it last year on my 3ds vc. I might have completed it twice in a row but I'm pretty sure I used warps both times.