On the eve of the American Civil War in 1861, Scarlett O'Hara lives at Tara, her family's cotton plantation in Georgia, with her parents and two sisters. Scarlett learns that Ashley Wilkes—whom she secretly loves—is to be married to his cousin, Melanie Hamilton, and the engagement is to be announced the next day at a barbecue at Ashley's home, the nearby plantation Twelve Oaks.
In Stockholm, Sweden, journalist Mikael Blomkvist, co-owner of Millennium magazine, has lost a libel case brought against him by businessman Hans-Erik Wennerström. Lisbeth Salander, a brilliant but troubled investigator and hacker, compiles an extensive background check on Blomkvist for business magnate Henrik Vanger, who has a special task for him. In exchange for the promise of damning information about Wennerström, Blomkvist agrees to investigate the disappearance and assumed murder of Henrik's grandniece, Harriet, 40 years ago. After moving to the Vanger family's compound, Blomkvist uncovers a notebook containing a list of names and numbers that no one has been able to decipher.
Lorenzo "Shakes" Carcaterra, Thomas "Tommy" Marcano, Michael Sullivan, and John Reilly are childhood friends in Hell's Kitchen, New York City in the mid-1960s. The local priest, Father Robert "Bobby" Carillo, plays an important part in their lives and keeps an eye on them. However, early on they start running small errands for a local mafia gangster, "King" Benny.
Artist Jennifer Spencer and her sister are raped by a group of boys, after being betrayed by female friend Ray Parkins. The brutal rape leaves Jennifer's sister permanently catatonic. Ten years later, Spencer seeks revenge. She kills one of the rapists (George Wilburn) with two shots—one in the groin and one in the head—from a .38 snubnosed revolver. Spencer then leaves San Francisco because of the subsequent police investigation. Once relocated in the town of San Paulo, Spencer begins restoring its boardwalk's historic carousel near the beach where the rapes occurred.
Psychiatrist Dr. Miranda Grey (Halle Berry) works at a mental hospital and has a car accident after trying to avoid a girl (Kathleen Mackey) on a road during a stormy night while driving back home. She rushes to try to help the girl. The girl turns out to be a ghost and possesses Miranda's body by burning her after she extends her hand to the girl. Miranda loses consciousness. Miranda next wakes up in the very hospital she works for, but as a patient treated by her co-worker, Dr. Pete Graham (Robert Downey, Jr.). Drugged and confused, she remembers nothing of what happened after the car accident. To her horror, she learns that her husband Douglas (Charles S. Dutton) was brutally murdered and that she is the primary suspect. While Miranda copes with her new life in the hospital, the ghost uses her body to carry out messages (most noticeably, she carves the words "not alone" into Miranda's arm), which leads her former colleagues to believe Miranda is suicidal and is inflicting the wounds on herself.
Philadelphia, 1999. In a violent home invasion, engineer Clyde Shelton (Gerard Butler) is forced to witness the rape and murder of his wife and young daughter by Clarence James Darby (Christian Stolte) and his accomplice Rupert Ames (Josh Stewart). Prosecutor Nick Rice (Jamie Foxx) is unable to use DNA evidence to securely convict both accused. Unwilling to take a chance on lowering his high and yet unbeaten 96% conviction rate, he chooses to make a deal with Darby (the actual murderer), letting him plead guilty to a lesser charge, in return for testifying against Ames. Ames is falsely found guilty of masterminding the break-in and both murders and is sentenced to death. Shelton feels betrayed by Rice's actions, as he had pleaded with him not to make the deal and to at least try convict both of them, and because he chose to release the actual killer. Darby serves his shortened sentence and is released just a few years later.
After celebrating at a drinking party with his close friends, Tun (Ananda Everingham), a photographer, and Jane (Natthaweeranuch Thongmee), get into a car accident. Jane hits a young woman. With much fear, Tun prohibits her from getting out of the car: they drive away, leaving the girl lying on the road.
In December 2002, Mikael Blomkvist, publisher of Millennium magazine, loses a libel case involving allegations he published about billionaire financier Hans-Erik Wennerström. He is sentenced to three months in prison and a hefty fine. Lisbeth Salander, a brilliant but damaged surveillance agent and hacker, is hired by Henrik Vanger, the patriarch of the wealthy Vanger family, to investigate Blomkvist. Vanger then hires Blomkvist to investigate the disappearance of his niece, Harriet, who vanished on Children's Day in 1966. Vanger believes that Harriet was murdered by a family member.
A group of scientists are killed by a mutant named Pluto (Michael Bailey Smith). Later, Bob Carter (Ted Levine) and his wife, Ethel Carter (Kathleen Quinlan) are traveling from Cleveland, Ohio to San Diego, California for their silver anniversary. With them are their teenage children Bobby (Dan Byrd), and Brenda (Emilie de Ravin), eldest daughter Lynn (Vinessa Shaw), Lynn's husband Doug Bukowski (Aaron Stanford), their baby daughter Catherine (Maisie Camilleri Preziosi), and their German Shepherds, Beauty and Beast.
In 1931, the Bondurant brothers—Forrest, Howard and Jack—are running a successful moonshine business in Franklin County, in the Virginia Piedmont region. They use their gas station and restaurant as a front for their illegal activities, and their friend Cricket Pate assists them in their endeavors. One day, Jack witnesses mobster Floyd Banner shooting a competitor, and Jack and Floyd exchange looks.
Ben Shaw (Joshua Jackson) and his new bride, Jane (Rachael Taylor), leave New York for Tokyo, Japan, where Ben has a job as a photographer. While traveling, Jane hits a girl in the middle of the wilderness, running over her. They find no body or even a trace of blood and decide to leave, thinking the victim was all right. They later start to find mysterious lights in their photos, which are later identified as spirit photography by Ben's assistant, Seiko Nakamura (Maya Hazen). Jane begins to have eerie dreams and visions as if they are trying to tell her something, and senses a haunting presence stalking them. Ben begins to complain of severe shoulder pain, and his friends begin to comment he's looking bent and hunched over, though the doctor can find no cause. Seiko takes Jane to her ex-boyfriend, Ritsuo (James Kyson Lee), whose career is to investigate paranormal activities, and he tells them that the lights are spirits, manifestations of intense emotions trying to communicate. At a subway station, Jane spots the ghostly presence of the girl she hit, causing her to believe that she killed the girl. Ben later also has a similar terrifying encounter. They go to a medium, Murase; however, Ben refuses to translate what Murase says, claiming he is a fraud.
Four Atlanta businessmen, Lewis Medlock (Burt Reynolds), Ed Gentry (Jon Voight), Bobby Trippe (Ned Beatty) and Drew Ballinger (Ronny Cox), decide to canoe down a river in the remote northern Georgia wilderness, expecting to have fun and witness the area's unspoiled nature before the fictional Cahulawassee River valley is flooded by construction of a dam. Lewis, an experienced outdoorsman, is the leader. Ed is also a veteran of several trips but lacks Lewis' machismo. Bobby and Drew are novices.
Paul Kersey (Charles Bronson) seems to have picked up the pieces of his life and moved on, and is now dating L.A. radio reporter Geri Nichols (played by Bronson's real-life wife Jill Ireland). They go to pick up Kersey's daughter Carol (Robin Sherwood) from the hospital, where her doctor says that despite traumatic catatonia, Carol has begun to speak again. Paul, Geri, and Carol spend the afternoon at a carnival. While waiting in line for ice cream, Paul gets pick-pocketed by five gang members (named Nirvana, PunkCut, Stomper, Cutter and Jiver). He catches up with Jiver, after a brief struggle, denies taking Paul's wallet. Paul lets him go.
A captive woman—forced to breed mutant children—gives birth to a stillborn. She is then killed by mutant leader Papa Hades (Michael Bailey Smith) for being unable to provide healthy offspring. Later, scientists working in the New Mexico desert are attacked by Letch.
Plastic surgeon Robert Ledgard was successful in cultivating an artificial skin resistant to burns and insect bites, which he calls "GAL", that he says he has been testing on athymic mice. He presents his results in a medical symposium but when he privately discloses he has also conducted illegal transgenic experiments on humans, he is forbidden to continue with his research.