The glitch in the quest with the giant tree, where if you don't activate the cutscene at the right time, you can't get to the tree's heart, because the game stops you, while trying to activate a cutscene that never comes. The only way I was able to complete that quest after that was to take the SUPER EVIL ending, and burn the tree down.
That, and on the PC version of Fallout 3, and Oblivion, my dev console button never works, so I couldn't noclip past it.
Although it is funny for Three Dog to give the whole Messiah spiel, just to go into a rant about how I'm a huge jerk for burning down the last tree in existence.