The movie opens with Peter Parker as a child, playing hide-and-seek with his father, as he discovers his father's office has been ransacked. His horrified parents rush him out of the house, leave him with his aunt and uncle, and disappear.
Now, he is a picked-on nerdy teenager (Andrew Garfield), smitten with Gwen Stacey (Emma Stone), still living with his Aunt May (Sally Field) and Uncle Ben (Martin Sheen). He finds his father's briefcase, containing pictures, clippings, formulas, algorhythms, and an Oscorp staff badge. It seems his father worked with the brilliant Kurt Connors (Rhys Ifans) before he and his wife died in a mysterious plane-crash.
Peter goes to Oscorp, pretending to be an intern, discovering that Gwen Stacy already works there. He meets and impresses Connors, an expert on cross-species genetics, reptiles, and limb replacement. Connors has one arm. Snooping about, Peter stumbles into a lab where spiders are being experimented on, and he is bitten. On the subway home, he finds himself on the ceiling of the subway car, objects sticking to his fingers. His awkward movements cause a fight to break out and he beats the crap out of several tough-guys. The next morning he has immense strength and enhanced senses.
He humiliates the class bully on the basketball court, causing so much damage that Uncle Ben is called to the school. He gets the lecture about responsibility. Peter runs off, is attacked on the street, climbs the side of a building to escape. Uncle Ben goes looking for him on the mean streets and ends up dead.
Spider-Man is born, suit and all. The police--especially Captain Stacy (Denis Leary), Gwen's father--are trying to hunt him down as a dangerous vigilante. Meanwhile, Connors is about to be fired by Oscorp. He experiments on himself, re-growing his arm but turning into The Lizard.
The differences between this story and Sam Raimi's Spider-Man (based on a different comic-book series) are the emphasis on the back-story of Peter's orphaning, gorgeous blonde Gwen Stacy instead of gorgeous redhead Mary Jane as the love-interest, the details of Uncle Ben's death, Peter inventing instead of growing web-shooters, and The Lizard as the villain.
What is the same: Compelling actors, particularly Andrew Garfield, so realistic as a smart but bumbling teenager that you believe the superhero implausibilities; a brilliant, powerful, scary, and tragic villain, who is not Doc Ock, but I can still watch him all day; moments of real sentiment and humour, often at the same time; and wide-screen acrobatics in places high above New York City that are eye-popping, dizzying, and breathtaking. Pretty much what you watch a Marvel movie for.