The one from Fallout 3 where, while doing research for the Wasteland Survival Guide, you explode a bunch of Mole Rats, causing Moira to exclaim something along the lines of "Oh, those poor little Mole Ratties". It's just the combination of the weird cutesy nickname and that accent cobbled together with the setting. Got a chuckle out of me every time!
Going to Nipton in FNOV for the first time, seeing the smoke from a distance, and then the total destruction and crucified people on the crosses. Then meeting the dog-faced guy from Ceasars Legion as he left town. Come Fly with Me was also awesome. Saving Megaton (never blew it up), and discovering Ant Man (I think that was his name) somewhere in a little town in the NW part of the map.
Can't remember if it is an actual quest or something you can just do but finding all the parts of the Survivalists story in the NV Honest Hearts DLC, just loved all that as I loved everything in that DLC in general.
I kinda liked the idea of purifying water in FO3 ( the main quest more or less )