Tobey Maguire (Spider-Man / Peter Parker), Kirsten Dunst (Mary Jane Watson), James Franco (New Goblin / Harry Osborn), Thomas Haden Church (Sandmann / Flint Marko), Topher Grace (Venom / Eddie Brock), Bryce Dallas Howard (Gwen Stacy), J.K. Simmons (J. Jonah Jameson), James Cromwell (Captain Stacy), Cliff Robertson (Ben Parker), Ted Raimi (Hoffman), Rosemary Harris (May Parker), Theresa Russell (Emma Marko), Bill Nunn (Joseph 'Robbie' Robertson), Bruce Campbell (Oberkellner), Dylan Baker (Dr. Curt Connors), Elizabeth Banks (Betty Brant), Elya Baskin (Mr. Ditkovitch), Mageina Tovah (Ursula Ditkovich), Steve Valentine (Fotograf), Willem Dafoe (Norman Osborn), Stan Lee (Mann am Times Square), Becky Ann Baker (Mrs. Stacy), Joe Manganiello (Flash Thompson), Michael Papajohn (Dennis Carradine / Autodieb)