Follow the Leader: The idea of the hero's Arch-Enemy personally killing a loved one of the hero was unprecedented when the story came out. The governing philosophy of superhero comic editors before was that such a line crossed risked making the hero ineffective. After this story, later writers introduced more stories of heroes failing their loved ones. Successors include Frank Miller's run on Daredevil which introduced Elektra who died at Bullseye's handsnote which admittedly did not stick but was treated in Miller's pages as if it definitely did stick, The Joker in The Killing Joke, A Death in the Family and other adaptations.
Jossed: A meta example: One of the early fan theories about this story was that its main purpose was to kill off the Green Goblin for good because the situation where he knew the secret of Spider-Man's identity was too dangerous to be allowed to continue. This, according to the theory, would have required a crime so heinous that readers would accept Norman Osborn's death as permanent and would not clamour for his return. But some time later Harry Osborn became the new Green Goblin and it turned out he too had found out that Peter Parker was Spider-Man. And he was allowed to survive without being made to forget...
Gwen was not originally the first choice to be the SacrificialLion. Gerry Conway and editor Roy Thomas first considered Aunt May, but later changed their mind because artist John Romita said that would leave Peter without a real motivation to maintain a secret identity (it also would have been too predictable). They later considered killing off Mary Jane, but at the time she was not important enough to make an impact on the readers, or even on Peter, who had proven highly resistant to her advances in previous stories. So they finally settled on Gwen Stacy, the actual love interest.
Mary Jane wasn't supposed to have closed that door at the end of #122. The original final page would have Peter lashing out at MJ but, instead of shutting the door, she would have returned to Peter's side and held him as he mourned. Gerry Conway thought Gil Kane version didn't have right emotional impact and allowed John Romita Sr. to redraw the scene.