Largest in-game surprise you have experienced?
I feel like I've told this story before, and if so I apologize. Back in college I was playing a game of Cyberpunk 2020. I was a fixer (which suited by personality at the time well), and was in a typical "heist" group composed of two Solos, a Tech, a out-of-place Rockergirl, and myself. The set-up was pretty typical: we can be hired by somebody to break into some corporate building and steal something (in case you wondered where Shadowrun came from, it was because a lot of people were playing Cyberpunk 2020 this way).
Right before the day of the big heist, I get a call from the GM telling me he wants to do a bit of in-person roleplaying on the side from the group, so I agree to have my PC meet some NPC contact of his. That contact tells him that he's gotten word that a member of the group has sold the rest of us out and will turn on us during the heist. I immediate go into meta-gaming mode and determine that it is Paul's PC, because Paul is the kind of guy who would do that to his gaming group. You know the type: he's the guy who would pocket dungeon treasure secretly because he could. So I figure I can let the heist spool out enough until I get some clue of Paul's duplicity and then drop the hammer on him.
Our plan was to have the two solos and me go into the corporate building (I had all the lockpicking skills) while the Tech and Rockergirl wait outside in a hovering AV4. It all goes pretty well until while we are in the bowels of the building the GM tells us that suddenly alarms start going off. "It's him!" I screamed while pointing a squirt-gun prop at Paul, "It's all his fault! I'm going to shoot you in the head!"
Paul looked at me with wide eyes and said, "Rob, you have lost your god damn mind."
"I know it's you! One of my contacts said one of us betrayed us and I know it's you! We have to get out of here!" I turned and said to the GM "I radio [the Tech] to bring the AV4 around to the closest window so we can hop on board."
"I'm afraid I can't do that," said the Tech's player. "[The Rockergirl] and I are long gone."
Then the Tech's player informs us that they decided to sell us out, and have left us to our fates. In the end, the two Solos and my Fixer were all killed by security guards, and the campaign ended. If there's a moral to this story it might be to always watch out for Genre Fiends in Cyberpunk RPG's, because for them having things go badly is just how the game should go.