Contra on the NES.
Resident Evil 4.
I believe I finished it 27 times, if I'm not mistaken. When I used to speedrun it, it was right after the game was released, a new technique was out like every day and it was hard to keep the run updated. I believe I still have the saves on my memory card, it has the number of replays.
I have forgotten the amount of times I have finished Metal Gear Solid. I have also beaten Resident Evil 4 and Neverwinter Nights a lot. Other then that there would be a whole mess of games with 2-3 play throughs. I tend to move on after I beat a game and not go back.
SMB3 or Mega Man 2... I got both when they released on the NES and... as was common back then as a kid growing up - they were the only games I had for a good while (meaning new, still had older stuff but these were replacements for that)... these two never got old. Also throw NES Contra into that mix also - I beat that every couple of weeks, usually on mute listening to the radio and killing time. I suddenly realize just how ancient I am... Link To The Past is CLOSE - but took longer to play through so it wouldn't quite measure up in sheer volume of playthroughs. Literally these (and Mega Man 3 once it came out - the last one I really played until the recent retro releases and the Anniv Collection) somewhere in the hundred range of playthroughs.
" MGS4 -- 10 times. By the end, I was beating it in 3 and a half hours. "So, you were good enough to get the Big Boss emblem? I played through that game 5 and a half times (normally I would stop where you face Vamp).
But Pokemon RSE-played Ruby thrice, Sapphire twice, and Emerald twice.