Tired of Jameson giving Spider-Man the rap for all the crime in New York, Peter decides to give up the superhero business once and for all. However, his biggest fan, a little girl named Tyina, is determined to make Spider-Man change his mind.

Spider-Man loses his memory and becomes partners in crime with Dr. Octopus.

Harry's father, Norman Osborn, disappears after an explosion at his chemical plant. Spider-Man's search for his friend's father, one way or another, meets with complications, namely an airborne fiend who calls himself the Green Goblin.

While a gang of jet-pack wearing thieves run by Jackson Weele, an ex-pilot in a rampaging gyro-wheel, plunder the city, Peter tries to deal with his alter-ego giving him competition with Felicia Hardy. Meanwhile, a good kid with a criminal record, Robert Farrell, tries to help his ailing mother by using his science-savvy and the gang's technology to arm himself as the Rocket Racer. While Spider-Man's fighting crime, the mysterious "Jason Phillips" starts to make moves on Felicia.

Peter is framed for a crime he didn't commit and it's up to blind lawyer Matt Murdock to prove his innocence, who is also known as the Man Without Fear, Daredevil.

Spider-Man and Daredevil manage to recover the disk that can clear Peter Parker's name. However, when Matt Murdock hands the disk over to the FBI, detective Terry Lee discovers agent Choi may not be working for the right side when she hands it over to Richard Fisk. After learning that Aunt May is in the hospital, Peter risks his life to go visit her, but he and Mary Jane are kidnapped when the Chameleon disguises himself as Anna Watson. With Peter and the disk in the hands of the Kingpin, Daredevil must stop the criminal mastermind and clear Peter's name.

Worried that the Kingpin is going to eliminate him after the botched framing of Peter Parker, Alistair Smythe arranges a meeting with Spider-Man to give him information about the Kingpin. When Spider-Man arrives, he discovers Smythe has been turned into a spider-slaying cyborg. However, when his programming malfunctions, he goes after the man he feels responsible for his father's death, Norman Osborn. Peter must fight a crazed Smythe, as well as his feelings, after he discovers Mary Jane, the woman he loves, and Harry, his best friend, are engaged.

Robbie Robertson is losing his son, Randy, to a gang of thugs lead by Tombstone. When this harder-than-stone hitman tries to use his history with Robbie to kill a story about his new boss, Alicia Silvermane, he runs afoul of Spider-Man. Both discover Robbie's bond with his child and his ethical resolve is mightier.

Under the psychiatric care of Dr. Kafka, Eddie Brock has come to believe that Venom is a figment of his imagination. Then Baron Mordo tempts Eddie to a reunification with the alien symbote that makes him as powerful as Venom.

Spider-Man and Venom must put aside their differences and help Iron Man stop Carnage and Baron Mordo from releasing Dormammu.

Ex-employee of Stark Industries, Dr. Jonathan Ohn, invents a portable interdimensional technology that accidentally makes him the living embodiment of a portal. Calling himself the Spot, he tries to steal money to fund his research. But his unstable invention has created a vortex that threatens to engulf New York.

When Dr. Ohn's Time Dilation Accelerator falls into the wrong hands, all the criminal minds of the city vie for the portal technology. Peter and Mary Jane are celebrating Felicia Hardy's engagement to Jason Macendale when they overhear plans for a major heist.

Peter Parker and Mary Jane are finally a couple, but their happiness is short-lived as the Green Goblin, armed with a Time Distorter and the true identity of Spider-Man, seeks to destroy the web-slinger by any means necessary.