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NOTE: This spoiler was submitted by Nash.

The film opens with Megamind (Will Ferrell) falling to his death, while he recounts the events leading up to this point. As an infant his parents rocket him away from his home planet on an escape pod just before it gets sucked into a black hole. As his shuttle was leaving, another shuttle which holds the baby Metro Man (Brad Pitt) left from a neighboring doomed planet and also heads toward Earth. Baby Metro Man gracefully landed in a wealthy family home while baby Megamind crashed landed in the Metro City Prison for the Criminally Gifted. The convicts raised baby Megamind, teaching the opposite of right and wrong. He showed he had a knack for building things and causing destruction. After a few years, he was escorted from prison to attend school where he met a young kid Metro Man. During Megamind's days at school he was rejected by all the students while Metro Man won their affections with demonstrations of his powers. When Megamind couldn't take it anymore he decided to accept his role as the bad guy and created a blue smoke bomb in the school house, which initiates the war between Megamind and Metro Man. Years have gone by and their war continues with Megamind losing all battles against Metro Man.

Metro City is about to open the Metro Man museum. Roxanne Richie (Tina Fey) a local news reporter and cameraman Hal (Jonah Hill) are on scene. Minion (David Cross) Megamind’s childhood friend and henchmen drives in his invisible car and kidnaps Roxanne. Meanwhile Megamind, is in prison about to receive a gift watch from Metro Man (but was actually from Minion) by the Warden. The Warden decides to keep the watch but Megamind tricks the Warden and frees himself from prison. Both Megamind and Minion rendezvous in their secret lair with Roxanne in tow. Metro Man makes his grand entrances to the opening of his museum.

Back in Megamind’s lair, Megamind attempts to intimidate Roxanne with fear but fails miserably. He then crashes the Metro Man celebration and goads Metro Man to finding him at the abandoned observatory building.

Metro Man ends up in the wrong observatory tower trapped. Metro Man discovers he lost his powers due to the dome being made out of copper which shocks Megamind. Megamind unleashes the death-ray on Metro Man finally ending his nemesis reign. Megamind celebrates his victory by causing havoc and graffiti in the city. With no one stopping his reign of terror, he becomes bored without purpose. He goes to the Metro Man museum to pay his respects to his nemesis, while at the same time Roxanne is also visiting the museum. Megamind and Roxanne overhear each other and realize they were not alone. Megamind quickly uses a hologram device to disguise himself as the Museum’s curator Bernard  whom Roxanne is acquainted with. After a few exchanges Roxanne suggests to Bernard (Megamind) that heroes are not born but made which gives him an idea.  Back in Megamind’s lair, Megamind uses the DNA from Metro Man’s cape to develop a serum to creating a new superhero. He receives a call from Roxanne thinking he is Bernard and tells him she has found Megamind’s lair at another abandon observatory tower. Megamind immediately panics and uses the Bernard hologram disguise.

While in his lair both Roxanne and Megamind became attracted to each other. An accident from Megamind’s robots causes the Super serum to be thrown into the vent ducts and accidentally injected into Hal. Megamind then tracks down Hal and manipulates him with a disguise that he’s Hal’s Space Dad and has granted him superpowers to defeat Megamind to be Metro City’s new hero. Megamind as SpaceDad trains Hal who becomes Titan to properly use his superpowers. At the same time as Bernard develops his relationship with Roxanne, Minion begins to notice Megamind’s interest in Roxanne and the two have an argument over it which causes Minion to leave. Hal decides to show off his abilities to Roxanne only to be rejected which infuriates Hal. Roxanne manages to meet with Bernard (Megamind) for dinner. As they are kissing, Megamind’s hologram dissipates to revealing his true form, shocking Roxanne who immediately leaves. With Megamind alone and depressed decides to take out his frustrations with his battle with Titan (Hal) only to find he did not show up for their scheduled fight. Megamind finds Titan playing videogames and discovers Titan would rather be a villain than a hero. He asks Megamind if they can be a team but Megamind refuses and reveals the truth to Titan which enrages him into a fight. Megamind attempts to use a copper prison on Titan but discovers it wasn’t his weakness.

Titan defeats Megamind and nearly kills him but Megamind narrowly escapes.

As Titan causing destruction in Metro City, Megamind, realizing that Metro Man can’t be dead, seeks Roxanne’s aid to find Metro Man. Roxanne and MegaMind go to the old school house where Metro and Mega both attended and discovered it was Metro’s hidden base. They both discover Metro Man is alive and well. He faked his death because he was bored and he decided to retire from the superhero business to be involved with music. Roxanne tries to convince Megamind to be the one to carry the torch but he refuses due to his role of being the villain. Megamind then turns himself in to the Metro City prison while Roxanne attempts to stop Titan. Roxanne calls Titan to convince him there was still good in him but instead Titan ties her up in Metro City tower. Titan calls out Megamind to show himself and points the camera on Roxanne.  Roxanne begs Megamind to save the city. Megamind with the help of Minion frees himself from prison and stops Titan. Megamind uses the device which gave Titan his powers to remove them and saves Metro City and Roxanne with the use of brains and trickery. The city declares Megamind to be the defender of Metro City and rebuild the museum to honor Megamind.

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