Game: Skyrim - Legendary Edition (Modded)
Platform: PC
I made the mistake of storing hundreds of unique Weapons, Items and Armor sets in a chest at Fort Dawnguard, rather than just buying a home like a normal person. One day they all just vanished, I'm assuming it happens when you upgrade the Fortress or when items replenish themselves after a certain amount of time passes.
I was roleplaying and really got into it, sorta like a guy who's obsessed with his job, that he doesn't have a life outside of it. Once the Vampires went bye-bye, my Character was gonna have to struggle with making a real life for himself. Losing all of my hard-earned gear, made me just wanna beat the Vampire Boss and get it over with.
It sucks because, up until that point, I was having a great time with the game (it was the best video game session I'd ever played). The bugs and crashes weren't enough to discourage me, though I do remember some of the more awful ones, but... it was ultimately an in-game mechanics that chased me away.
Side Note: Luckily, Skyrim modding is in a much better place these days; game-breaking bugs/ glitches and crashes are nearly nonexistent. It also helps that Skyrim itself is in a much more stable and playable state.