Spider-man 3 really killed off a lot of interest for this franchise.
For me it wasn't Spider-Man 3 that did it, as I didn't see that movie as the disaster that most did. No, my interest waned as soon as the studio decided there was a need to reboot the whole thing afterwards. I would much rather have seen what Sam Raimi's Spider-Man 4 would have looked like. We almost certainly would have gotten the exact same villain.