If I had to only pick one? I'd probably go with the first Resident Evil on the PS1.
I still have fond memories of playing the original RE trilogy as a little kid in the late 90's. Granted, I was probably way too young to play M-rated games back then, but still, it was awesome.
Overall, I'd say it would depend on the generation or era in question.
There's several games I'd like to be able to experience for the first time all over again.
Fourth Generation: Super Mario World, Super Street Fighter II: Turbo, Mortal Kombat II
Fifth Generation: Syphon Filter 2, Crash Bandicoot: Warped, Spyro 2: Ripto's Rage, CarnEvil, Dino Crisis 2, Digimon World 2, or any of the first three Resident Evil games
Sixth Generation: Grand Theft Auto III, Devil May Cry 1, Morrowind, VTM Bloodlines, Dynasty Warriors 4, Dead or Alive 2: Hardcore
Seventh Generation: New Vegas, Mafia II, Red Dead Redemption, Time Crisis 4, Skyrim
Eighth Generation: Final Fantasy XV, Resident Evil 2 Remake