Trivia for the film:
- Hey, It's That Guy!:
- Ash from Evil Dead appears again, this time keeping Spider-Man from seeing Mary Jane's play.
- Joel McHale as the bank teller, and Donnell Rawlings (Ashy Larry) as the witness of the pizza "heist" (the source of this film's Memetic Mutation, by the way). Apparently, Dave Chappelle himself was supposed to be the guy in the elevator, but for whatever reason he was replaced by Hal Sparks of Queer as Folk/Best Week Ever fame.
- Joel would reference his cameo three years later in an episode of The Soup with a spoof trailer of Spider-Man 3, where his bank-teller character becomes a Magnificent Bastard.
- Why is Bones working as a receptionist?
- Daily Show's Senior Fire Nation Correspondent Zhao as Mr. Aziz.
- Raymond, Doc Ock's lab assistant, is Jin-Soo Kwon
- One of Mr. Ditkovich's buddies playing poker with him is Edgar Stiles.
- Elijah is John Jameson.
Trivia for the game:
- Celebrity Voice Actor: The game has the voices of Tobey Maguire (Spider-Man), Kirsten Dunst (Mary Jane), Alfred Molina (Dr. Octopus), and Bruce Campbell as the Narrator. Additionally, whilst some movie characters are not voiced by their film counterparts, they are played by notable character actors such as Mindy Sterling (Aunt May) and Susan Egan (Rosalie Octavius).
- Hey, It's That Voice!:
- Tobey Maguire, Kirsten Dunst, and Alfred Molina reprise their respective roles from the movie as Spider-Man, Mary Jane Watson, as Doctor Octopus.
- As in the game to the first movie, Josh Keaton fills in for James Franco as Harry Osborn.
- James Arnold Taylor is Mysterio.
- John DiMaggio is the Rhino.
- Mindy Sterling (Frau Farbissina, Lin Beifong) fills in for Rosemary Harris as Aunt May.
- Michael Beattie reprises his role from the first game as the Shocker.
- What Could Have Been: The 2003 trailer sported a more cel-shaded style, and showcased the Lizard, who never made it into the game (though there were reptile men of sorts in the game, though only in an unlockable bonus mode).