Peter Parker plans to propose to Mary Jane Watson, who has just made her Broadway musical debut. A meteorite lands near Central Park, and an extraterrestrial symbiote emerges and follows Peter to his apartment. Meanwhile, police pursue escaped prisoner and robber Flint Marko, who visits his wife and sick daughter. The chase resumes, and Marko falls into an experimental particle accelerator that fuses his body on a microscopic level with the surrounding sand, transforming him into Sandman. Harry Osborn, seeking vengeance for his father's death in the first film, attacks Peter with new weapons based on his father's Green Goblin technology. The fight results in Harry receiving amnesia, erasing his memory of Peter as Spider-Man as well as his vengeance.
During a festival honoring Spider-Man, Peter kisses Gwen Stacy for show, infuriating Mary Jane. A newly superpowered Marko robs an armored car nearby and Spider-Man confronts him. Initially warning him to leave to avoid a fight, Marko easily subdues him and escapes. Later, NYPD Captain George Stacy tells Peter and Aunt May that Marko was Uncle Ben's killer, and the deceased Dennis Carradine was only Marko's accomplice. While a vengeance-obsessed Peter sleeps in his Spider-Man costume, the symbiote takes over his suit. Peter wakes up hanging from a skyscraper, discovers his costume has changed and his powers have been enhanced, but the symbiote brings out Peter's dark side over time. Wearing the new black suit, Spider-Man locates Marko and battles him in a subway tunnel, the symbiote influencing him to fight more brutally. He discovers water is Marko's weakness and breaks a water pipe to reduce Marko to mud, washing him away and believing him to be dead.
Peter's changed personality alienates Mary Jane, whose career is floundering, and she finds solace with Harry. Harry recovers from his amnesia, and, urged by a hallucination of his dead father, threatens Mary Jane into break up with Peter. After Mary Jane tells Peter she loves somebody else, Harry meets with Peter and claims to be "the other guy." Later, Peter, wearing the black suit, confronts Harry, and spitefully tells him his father never loved him, done with attempting to prove his innocence. After a violent fight, Harry throws a pumpkin bomb at Peter, who deflects it back, disfiguring Harry's face.
Under the symbiote's influence, Peter exposes photography rival Eddie Brock by proving his fake photos depicting Spider-Man as a criminal. Soon afterwards, to make Mary Jane jealous, Peter brings Stacy's daughter, Gwen to the nightclub where Mary Jane now works, but Gwen catches on and leaves. Peter brawls with the bouncers and, after accidentally attacking Mary Jane, he realizes the symbiote is corrupting him. Retreating to a church bell tower, he discovers that he cannot remove the suit, but that the symbiote weakens when the bell rings. Peter removes the symbiote and it falls to the lower tower, landing on Brock, who had been praying for Peter's death. The symbiote bonds to Brock's body, transforming him into Venom. Brock then finds Marko, and convinces him to join forces together to defeat Peter.
Brock hijacks Mary Jane's taxi and hangs it as bait from a web hundreds of feet above a sand-filled construction site while Marko keeps the police at bay. Peter seeks Harry's help, but is rejected. While Peter battles Brock and Marko, Harry learns the truth about his father's death from his butler, and goes to help Peter as he is being overpowered, resulting in a battle between the four. Harry subdues the Sandman before assisting Peter against Brock. In the ensuing confrontation, Brock attempts to impale Spider-Man on Harry's glider but Harry intervenes, taking the blow and is mortally wounded. Recalling the symbiote's weakness, Peter uses metal pipes to create a sonic attack, weakening Venom and allowing Peter separate Brock and the symbiote. Peter activates a pumpkin bomb from Harry's glider to destroy the symbiote but Brock dives in and the bomb kills them both.
Marko explains to Peter that he committed robberies to save his dying daughter and takes Peter back to the night his uncle Ben died. While Ben was convincing Marko to go home after getting him out of his car, Carrdine hit Marko's elbow, shooting uncle Ben in an accidental knee-jerk reaction, plaguing Marko with guilt since. Peter forgives Marko, who dissipates and floats away peacefully. Peter rejoins Mary Jane and a dying Harry. The two reconcile as Harry dies beside his two best friends. After Harry's funeral, Peter and Mary Jane reconcile their relationship at the nightclub where the two have a romantic dance.
What character has just made their Broadway musical debut?
Mary Jane Watson