I was a programmer on a game that had a really bad bug, a jrpg where something like 4 hours into the game, you got a quest to find a hidden object, that you could only find by clicking on a wall with a decoration that fit the clue. If you talked to the wrong person after accepting the quest, the object wouldn't be there, so you couldn't finish the quest and progress through the game. Since the quest is to find the object, and it wasn't explicitly visible in the world, you wouldn't know that you couldn't collect it, so you would just think you couldn't find it. If you saved your game in that state, you were screwed, had to start the whole game over.
Two things that made the bug especially bad: the person to talk to who messed the quest up, was a nurse who stood next to you when you continued after dieing, so there was a decent chance you would talk to her. Second, this was in the age of cartridges (Gameboy Color), so it couldn't be patched. It was fixed...for a second cartridge run after the first few hundred thousand cartridges had been manufactured and put on shelves.