Norman Osborn - the Green Goblin - was gone, his best friend was fatherless, Uncle Ben did what all Uncle Ben's do, etc.. It was all very sad. In Spider-Man 2, we see a Spider-Man without his powers.
Sam Raimi's Spider-Man 4 is one of the great "what-ifs?" in superhero/comic book movie history. Tobey Maguire and Kirsten Dunst never got their swan song in the roles of Peter Parker and Mary Jane ...