Spider-Man 2099's dive down an elevator shaft to save Mary Jane.
The fact they included MJ in the game at all was this for a lot of people. Likely due to the fact that the game seems to completely ignore One More Day, which was in full force and deeply unpopular in Spidey's comics.
Amazing Spider-Man vs. Atrocity and Spider-Man 2099 vs Peter Parker 2099 SIMULTANEOUSLY at the end of the game.
Spider-Man 2099's utter Curb-Stomp Battle against Anti-Venom after Amazing Spider-Man dies and is placed in a regenerative pod.