The movie opens with a close-up on fingers furiously typing on a keyboard. Files are being deleted from a system. A bespectacled figure checks vials, some of which feature the skull and crossbones. A shot reveals it's Peter Parker's father, Richard Parker (Campbell Scott). Suddenly, his computer access is cut off and he can't complete his mission to destroy the project files. Richard dashes from the Oscorp building on his way home to Peter and his wife, Mary (Embeth Davidtz).
Richard is recording a message with a webcam. "People will say I'm a monster for what I've done." He hears Peter call for him and cuts his message short. Rushing up from the basement, he sees that the house has been ransacked. Someone is looking for the files he took. A car pulls up as Mary says goodbye to Peter. Richard grabs her away. Peter is clearly distraught. He touches Richard's hand for one last time and stares at them from the front door.
Richard and Mary are on a private jet. Mary mentions that she has found somewhere safe for them to stay as Richard uploads project files from his laptop. He tries to reassure her, explaining that their life has been changed forever. Richard doesn't want to put Peter through that. Mary pops into the bathroom just as one of the flight crew steps out of the cockpit. Richard is very suspicious and wary of the guy's behavior.
Suddenly the crew guy pulls a gun and threatens Richard. He locks Mary in the bathroom and prepares to shoot Richard. As Richard uploads the file, Mary realizes something is wrong and bursts out. A struggle ensues and Mary is shot! Richard desperately overcomes the thug. Mary reminds Richard to finish the upload just as the thug roars back to life. They scrap back and forth as we see the pilot (Timothy Adams) is dead and the plane falls into a steep dive.
The thug shuts down the laptop again as Richard realizes his fate is sealed. Mary is dead; there's no getting out. However, the file upload to Roosevelt has to be completed. Richard shoots out a window and holds onto the laptop attached by a cable. The hitman flies out the window to his death and Richard confirms that the file is transferred. The plane plummets to its doom and cut to black.
Present Day: Music rings in as the camera follows Spider-Man falling to earth. A stunning sequence follows Spider-Man play-webbing his way through the city. He overhears a helicopter radio announcing a plutonium shipment under siege at Oscorp. Spidey swings into action to help. A big tow truck is being driven by a bald guy with a Russian accent (Paul Giamatti).
He's bashing lots of Manhattan vehicles as he tows/steals the Oscorp truck. Armed assistants set explosives to blow the hatch as the Russian rolls over police cars. Spidey swings impressively through buildings in hot pursuit. The goons (Dusan Hyska & Andrei Runtso) blow the hatch and hop into the van. There's a container of yellowish vials that are their target.
Spidey hops onto the tow truck and engages in some Spidey banter with the Russian (who clearly has no idea who he is). As the goons prepare to hijack the plutonium, we cut to a Oscorp employee, the socially inept geek Max Dillion (Jamie Foxx) stumbling through a crowd with an armful of blueprints.
Naturally, the prints get knocked from his hands and roll into the street just as Spidey and the Russian barrel around the corner. Spidey leaps to the rescue and prevents Max from being squashed by a cab.
Spidey hands him the plans and notes that he works at Oscorp before leaping away. The Russian, clearly ignorant of the dangers of radioactive material, slams into a bunch of cars, tossing the goons and the P-238 around in the van. Dozens of cop cars crash into the truck pinning it in. The goons burst from the van firing at the cops with automatic weapons. Strands of web shoot from above, yanking the goons and suspending them over the cops.
The Russian takes his chance to escape. The P-238 is bouncing all over the place as Spidey tries to avert disaster, catching, juggling and swinging like a chandelier. As he bounds out to recover one last vial, his phone rings. Gwen Stacy (Emma Stone) is at their high school graduation waiting for him. He's really late. As he playfully banters with Gwen he imagines that he sees her disapproving father riding by in an NYPD patrol car.
He remembers his broken promise to leave Gwen alone (from the first Amazing Spider Man film). Gwen is called up to deliver her valedictory speech. Peter isn't there. Cut back to the truck chase. The next sequence bounces back and forth between the speech and Spidey trying to stop the truck. Parker's Spider sense triggers into a slow motion shot as he leaps over a bus to protect some pedestrians.
Finally, Spidey subdues the Russian, grabs the P-238, makes it to graduation and kisses Gwen on stage. (Note: Spider Man and comic book creator Stan Lee has a cameo as an elderly man at the graduation who sees Peter change out of his Spider Man costume). Aunt May (Sally Field) takes pictures of the new graduate before sending him off with Gwen. They make a date for 8:00 pm.
Peter catches a glimpse of Captain Stacey standing with his family and hears his voice in his head. That evening, Peter shows up to the date, but won't come into the Chinese restaurant that Gwen and her mother and siblings are at. Gwen meets him at the door and they talk again about her dad and the promise Peter made. Peter is torn, but Gwen really isn't having it. Peter loves her, but he couldn't handle losing her because of his actions. Gwen decides to break it off. She's done.
The next morning, Peter is on another visually stunning city patrol. Falling and swinging as the wind ripples his Spidey suit. As a radio call-in show plays in the background, Spidey rescues a grade school kid and his science project. He encourages the kid, much like he did with Max at the beginning of the movie. During an extended montage, a talk radio debate rages while he saves a girl, changes clothes, saves a bodega and mingles with costumed New Yorkers. Of course, he still keeps an eye on Gwen every now and then.
After a cute scene with Aunt May, we cut to Max Dillon, who has really flipped out after his chance meeting with Spider-Man. He seems to have created an alternate Spidey persona with whom he engages in a meticulously crafted fantasy. Oscorp is developing a new power grid system and Max is part of the team. Max's delusion may have spilled over into his work life too.