Off the top of my head, in no particular order:

1. If you kill Gale and ignore the immediate convo about rezzing him, it results in a game over 3 days later.
2. Let a Vampire feed on you and don’t stop him in the two attempts.
3. Fuck Around and Find Out with damned Vlaakith, after listening to, watching and reading tons of stuff showing you that the Githyanki are nasty bad news, and several red flag warnings where the game explicitly warns you not to fuck around and find out.
4. Fail the Insight checks and trust the apprentice druid healer.
5. Trust the wounded Mind Flayer.
6. Fuck Around and Find Out with a desperate and angry explosives expert gnome.