You can seperate it into handheld and home consoles if you want or just take one per generation. PC games also count if they fit into that era.

For me:

Gen 5 - Pokémon Crystal on GBC

Gen 6 - Pokémon Ruby on GBA, Tales of Symphonia on GameCube

Gen 7 - Probably Diablo 3 on PC with StarCraft 2 as a close second

Gen 8 - Many games tied for 2 playthroughs: Persona 5, REmake 2, The Stanley Parable, Deltarune. I think the only one with "more" is Hades (which is kind of cheating)

Gen 9 - Haven't played anything multiple times yet unless I'm misremembering

Interesting topic. This was easier for me to figure out than I had originally thought it would be.

Gen 4 - Sonic 2 or Sonic 3 & Knuckles on the Genesis / Mega Drive

Gen 5 - Super Mario 64 on the Nintendo 64

Gen 6 - Halo: Combat Evolved on the OG Xbox

Gen 7 - Halo 3 on the Xbox 360

Gen 8 - Minecraft on PC

Gen 9 - Vampire Survivors on PC

Overall, Minecraft would be my most played game with likely well over 1,000 hours. I used to stream nothing but it on Twitch from like 2014 to 2018 or 2019 before I got sick of it and now stream whatever single-player game I want to.

Gen 3 - Mega Man 2
Gen 4 - Super Mario World
Gen 5 - Super Mario 64
Gen 6 - Eternal Darkness: Sanitys Requiem
Gen 7 - Dark Souls 2
Gen 8 - Elden Ring
Gen 9 - Balatro

Gen 4: Sonic 2
Gen 5: Zelda Majora's Mask
Gen 6: Pokemon Firered/Emerald
Gen 7: Mario Kart Wii
Gen 8: Fire Emblem Awakening

Considering only relatively clear cases, this is my list of games worth mentioning:

• Metal Gear Solid
• Metal Gear Solid 2
• Metal Gear Solid 4

There isn't really anything clearly valid for me before that, and I don't think I've replayed anything enough after that to be worth mentioning - that, or it's not clear enough how I should count my 'replays'. This includes game like these:

• Spear of Destiny
• Doom
• Dynasty Warriors 2/3/5
• Titan Quest
• Minecraft
• Cities: Skylines
• Grim Dawn

But I guess depending on how you count 'replays', you could also include some of those games in my list.

4th gen. Never finished a game.
5th gen. Metal Gear Solid.
6th gen. Metal Gear Solid 2.
7th gen. COD 4: Modern Warefare
8th gen. Sekiro or Bloodborne with NG+s but The Witcher 3 for fresh runs.
9th gen. Stellar Blade.
PC: Minecraft or Theme Hospital depending on the definition of completed.

Oh wait. Gor 8th gen it's GTA5 thinking on it now, five playthroughs fresh.

Straight up FF6, Chrono Trigger and Suikoden 2 are it for me. I play them almost yearly.