- Madame Webb
- Aunt May Parker
- Anna Watson
- J. Jonah Jameson
- Norman Osborn
- Mary Jane Watson
- Harry Osborn
- Daredevil (Cameo) (In Alistair's memories)
- Richard Fisk (Cameo) (In Alistair's memories)
- Susan Choi (Cameo) (In Alistair's memories) (Final appearance)
- Eddie Brock (Cameo) (In Alistair's memories)
- Spencer Smythe (In Alistair's memories) (In cryogenic suspension)
- Black Widow Spider Slayer (In Alistair's memories)
- Tarantula Spider Slayer (In Alistair's memories)
- Scorpion Spider Slayer (In Alistair's memories)
At the Daily Bugle, Peter Parker notices in the paper that Mary Jane Watson and Harry Osborn are engaged. Peter then receives a call from Alistair Smythe, asking him to tell Spider-Man to meet him on a rooftop, because he has some incriminating evidence against the Kingpin, to show him. However, Smythe is caught by the Kingpin and immobilized. Kingpin reminds Smythe of his failures, how the Spider Slayer robots failed to kill Spider-Man, and how thanks to Smythe's incompetence resulted in Richard Fisk, Susan Choi and Chameleon facing jail time. Landon replaces Smythe as Kingpin's lieutenant then changes the former Kingpin lieutenant into something more horrid.
When Spider-Man arrives to meet Smythe, he is greeted by a humanoid, robot-like Alistair, who attacks him. Spider-Man is almost destroyed by Alistair, but is teleported away by Madame Webb, who tells him to think about why he must defeat his enemies, not how.
A programmed Smythe returns to the Kingpin, where Herbert Landon attempts to re-program him. However, Alistair is accidentally reprogrammed as per his memories, and he sets off in his hoverchair after Norman Osborn, whom he partially blames in his mind as responsible for his father's death. He heads to Oscorp towers, where Norman is celebrating Harry and Mary Jane's engagement. When Alistair arrives, he kidnaps Norman. Kingpin sents a retrieval unit to intercept him, but Mary Jane and Harry are accidentally taken as well. Knockout gas renders everyone inside unconscious.
After the retrieval unit arrives at Crime Central, an unconscious Smythe is taken back to the lab, Mary Jane and Harry are locked up, and Norman speaks to Kingpin when he regains consciousness. Kingpin explains to him how Spencer Smythe is still alive, and that he has placed him in cryogenic suspension ever since the beginning of his association with Alistair. Spider-Man is spying on the conversation, but is spotted by the Kingpin's men. Landon activates a newly programmed Alistair with a brand new hoverchair to defeat Spider-Man. Alistair almost destroys him, but Spider-Man tells him that his father is still alive. Smythe then turns on Kingpin, and having been told about his father he regains his own consciousness; the programming which prevents him from harming Kingpin or Landon wears off, and he attacks them.
Kingpin and Landon escape when the building begins to explode, Smythe rescues his father's cryogenic suspension unit, while Spider-Man saves Norman, Harry and Mary Jane. As Norman prepares to leave in a taxi with his family, Mary Jane hands her engagement ring back to Harry and asks Spider-Man if she can go on a trip web-slinging with him to clear her head. She tells Spider-Man that she has realized that she doesn't love Harry, and that she thinks she is in love with somebody else.