After his uncle's death, Peter and his Aunt May were forced to live on Social Security, so he earned a living selling photographs of Spider-Man in action to the Bugle, a local newspaper. Peter also began to use his powers to fight crime, though he remains a controversial figure. Spider-Man has defeated a vast number of costumed criminals, including the Kingpin, the Vulture, Electro, the Sandman, Mysterio, Dr. Octopus, the Green Goblin, Kraven the Hunter, the Scorpion, the Rhino, Venom and Carnage. To thwart his enemies, Spider-Man uses his superhuman strength, reflexes and equilibrium, the ability to cling to most surfaces, and a sixth sense that warns him of impending danger. Spider-Man's wrist-mounted web-shooters discharge thin strands of web-fluid at high pressure, which forms a very tough, flexible fiber with extraordinary adhesive qualities upon contact with air. The life of a superhero is not an easy one. His first love, Gwen Stacy, died during a fight against the Green Goblin. Other friends have also died, including Harry Osborn, son of the original Green Goblin; and Gwen's father, police Captain George Stacy. Peter's marriage to Mary Jane Watson ended in separation due to the stress caused by his superhero activities.

Both Tobey Maguire and Kirsten Dunst return for this sequel, and in fact have already agreed to appear in Spider-Man 3. Director Sam Raimi likewise returns, although he has yet to sign for the third film. Massachusetts-born actress Elizabeth Banks, who had a glorified cameo in the last film, is also reprising her role of Daily Bugle employee (and Peter Parker's potential love interest) Betty Brant. Raimi favorite Bruce Campbell has a role in Spiderman 2 as well. The plot is something of a secret, probably complicated the chaotic rewrites associated with this film. Alfred Gough and Miles Millar (Shanghai Noon, Shanghai Knights, Smallville) were originally hired to work on the script, but then David Koepp (Panic Room, Stir of Echoes, Spider-Man) was asked to produce his own script for Gough and Millar to rewrite. Next, this trio was axed in favor of Pulitzer Prize-winning author Michael Chabon, who wrote the novel, The Adventures of Kavalier and Clay. Chabon turned in his original draft into Sony, saying that "I thought it more or less rocked," but was then dumped for the producer Laura Ziskin's husband, Alvin Sargent, a well-known and highly-regarded script doctor.

The sequel begins 2 years after the end of the first film and features a conflicted Peter Parker who would rather make babies with his sweetheart Mary Jane Watson than remain a superhero. Parker graduated from high school in the first movie, so he is now a college student at New York City's (fictional) Empire State University. According to Tobey Maguire, "Peter Parker is still struggling with being responsible versus what he wants for his own life. Self sacrifice, being in love with Mary Jane and the difficulty in balancing being a super hero and being a young man going to school and being in love with a girl and trying to make money, and kind of a regular person's stuff. It's difficult for him, and of course they're extraordinary circumstances and it's very dramatic." Things get even more extraordinary for Parker with the appearance of multi-tentacled Doctor Octopus, a.k.a. Dr. Otto Octavius (Alfred Molina), an evil scientist with four huge mechanical limbs. Sony is pushing for Spider-Man 2 to be even bigger than the first film, with Jeff Blake, vice chairman of Sony Pictures Entertainment, commenting that the release date was moved to June 30th because "When you have an event movie that is so widely-anticipated, it makes sense to give it as wide a berth as possible during the lucrative summer season." Chimes in Avi Arad, head of Marvel: "We realized that we had set the bar extremely high with the first movie." Production began in February, 2003 at Sony's soundstages in Los Angeles on a budget of $200 million, although some sequences involving Chicago's El trains were filmed in November 2002.

Fan favorite Doc Ock was a brilliant atomic researcher who became criminally demented after a freak lab accident fused mechanical limbs to his chest while he was handling deadly radioactive substances. His nervous system was damaged by the tragic event, but he also gains the power to control his new tentacles with his mind. Columbia Pictures chairman Amy Pascal told the Hollywood Reporter that "Alfred Molina has a remarkable facility for everything from classic drama to mainstream comedy, and he is the ideal choice for Doc Ock. We wanted an actor that would bring irresistible depth and dimension to this role, and we are all tremendously excited to be working with Alfred." The London born actor made his big screen debut as the double-crossing guide who tries to steal the golden idol from Harrison Ford in 1981's Raiders of the Lost Ark, but soon ends up impaled. Molina has also appeared in Enchanted April, Maverick, Boogie Nights, Chocolat, Ladyhawke, Letter to Brezhnev, Not Without My Daughter, Dead Man, Magnolia, Species, Anna Karenina, The Man Who Knew Too Little, and Dudley Do-Right.