Big Sister, Bioshock 2. I heard the Little Sister say "Big Sister doesn't like you playing with me." I'm the kind of guy who reads Game Informer, so naturally, all I could think of was "Shit, shit, shit, shit, shit!!!!!"
...And then I actually fought with her. I had my back to a corner, high-ish ceiling, and enough Firestorm Traps (My name) to make the freakin' Pillar of Fire in the Old Testament seem like a joke. then I saw her. I hit her my main gun and a steam turret, and she walked into all my traps. She just kept coming. At this point my thoughts were more along the lines of "F***, F***, F***, F***, F***!!!!!!" Finally, I nailed her with the drill charge. On Fire. She disappeared. I laughed, relieved. I walked away from the wall, my hands shaking. I thought, "Wow, I actually beat Big Sister!" Then I screamed like a girl in fear.
Big Sister's giant needle protruded from my Big Daddy throat.
Apparently she crawled on the ceiling, got behind me without me noticing, and performed an assassination that would have made Ezio proud.
I never harvested another Little Sister again after that.