Executive Meddling - The original plan was to create extra material for each episode, then use it to edit each Story Arc into a movie for the DVD releases. But only the first arc was released like this before Sony switched to just plain episodes on DVD, leaving extra footage we might not ever see.
Doc Ock has two. Pre-breakdown is "D'awwwc Ock", post- is "DOCTOR OCTOPUS, LORD OF THE VAMPIRES" due to his rather vampire-esque attire in "Gangland".
Due to the various girls that Peter/Spidey attracts, fans have decided to rename the show "BITCHES LOVE SPIDER-MAN: THE ANIMATED SERIES".
I Knew It: In the first season, we are introduced to the Green Goblin. Most people by now know that Norman Osborn is the Green Goblin, and at first the show didn't do much to deny this, giving several indications that it was he. Then later that season, we were shown that it was in fact Harry Osborn. When Goblin made his return in the second season, the final episodes played up the idea that other people could be the Goblin, giving the audience some very serious misdirection. Of course, all of this was proven to be just subterfuge, as in the final episode it was revealed that the Goblin had, in fact, been Norman Osborn all along.
Adding to the confusion, of course, was the fact that Harry Osborn was also the Goblin in the comics for a while.
Name's the Same: A variant; Weisman has admitted that part of the reason Silvermane and Silver Sable are related here is because they both have "Silver" in their names.
Ricochet takes the name of another unrelated Marvel character for his superpowered identity.
The Other Darrin - After the first episode, Keith David is replaced with Kevin Michael Richardson in the role of Tombstone. In the Enforcers' debut, Clancy Brown did Ox's grunts, but when the Enforcers returned in season 2 and Ox actually speaks, he was voiced by Danny Trejo.
Screwed by the Lawyers: Unlike most cases of the trope, there was no malice behind the cancellation of the show, but victim of poor timing. After Disney's purchase of Marvel, Sony gave up the broadcasting rights of airing Spider-Man TV shows during negotiations to keep their film rights note Which are obviously far more lucrative. Rather than drafting up a new contract to continue the production of Spectacular Spider-Man, Marvel and Disney decided to just go forward with a new show instead.
Short Run in Peru - Canada aired the entire second season before the US even started on it. And then Disney put it on hiatus midway through…