Dean: The Zodiac?
Sam: Seven victims.Dean: No. Bass fishing, needlepoint ...that's a hobby, okay? Collecting serial-killer stats ...that's ...that is an illness.
Dean: That's some freaky stuff, man. It's a whole new side of you.
Sam: It's called true crime, Dean. It's a hobby.
Serial killer is a term generally used to describe someone who commits three or more murders at different times, and usually committed in different places. The term is used in this sense in Supernatural in relation to humans, although many vengeful spirits and demons would also fit this definition. In fact, Bela Talbot even refers to Sam and Dean as serial killers.
Sam Winchester is fascinated with serial killers. In 10.14 The Executioner's Song, Dean quizzes him on the murder statistics of different serial killers. In 11.05 Thin Lizzie, when Sam finds a case in the Lizzie Borden House and is keen to investigate, Dean says: "This has something to do with your freaky fetish for serial killers."
In 14.03 The Scar, Jody says that she had thought a serial killer was responsible for a series of deaths, and Sam states that it would be the first one in South Dakota since Robert Leroy Anderson, demonstrating his knowledge of true crime. Dean gives him a mocking look.
In the process of finding his family's murderer, Nick becomes a budding serial killer; at first only killing the people involved around the death's of his wife and infant son, but begins to have urges to kill innocent people.
In 1862, Jacob Karns killed 13 women. His spirit continued to kills people, feeding off repressed emotions until his silver hook hand he was tethered to was destroyed.
David Berkowitz is the name on the credit card that Sam gives to the nurse in the hospital to pay for Dean's treatment. There is an extremely famous person with the same name, the serial killer also known as "Son of Sam."
Dean comments when examining Andy's van "Not exactly a serial killer's lair, though. There's no... clown paintings on the walls, or scissors stuck in victims' photos. I like the tiger." Dean mentioning clown paintings is a reference to John Wayne Gacy, who was known to paint portraits of his alter ego "Pogo the Clown" while incarcerated.
H.H. Holmes is often called America's first serial killer. The number of his victims has typically been estimated between 20 to 100, and even as high as 230, however, the only verified number is 2. In 1893 he opened a hotel for the Chicago World's Fair and used it to trap, torture and kill his victims. It became known as the Holmes Murder Castle. In Supernatural, his ghost is haunting the apartment building which was erected over the site where he was hung. When the Winchesters are researching people killed at Moyamensing Prison, it is Sam who recognizes that Herman Webster Mudgett was H.H. Holmes real name.
After Doc Benton found the secret to immortality, over many years he would kill people for their body parts to keep himself alive. Sam and Dean are able to stop him by burying him alive.
Jeffrey was a postal worker with psychopathic tendencies, who was possessed by a demon who started killing people. After the demon was exorcised, Jeffrey eventually began killing on his own. Eventually he would hope to be reunited with his demon after performing a special ritual to summon exorcised demons. The demon, would however refuse to possess Jeffery revealing it is only a "recruiter" and has already unleashed Jeffery's potential. Dean later kills Jeffery while Nora Havelock exorcizes the demon.
Whitman Van Ness killed his fiance, and a number of other women. He died at the age of 40, and continued to haunt the Van Ness House, killing many people over the decades all the while uses the other trapped ghosts in the house to feed off of and become stronger.
Cain teleports to death row to visit one of his descendants; Tommy Tolliver. Before he was arrested, Tolliver killed nine people, but the state only arrested him for seven. Cain kills him and teleports away with his body.
While Sam and Dean visit death row to investigate Tolliver's disappearance, Sam comments on how he collects serial killer stats from watching movies from the true crime genre, including murders commited by the Zodiac and Dahmer.
Castiel discovers that Cain is committing genocide by killing off his descendants. "Culling one in ten of everyone." He kills people of varying ages and genders and buries their corpses in a plot somewhere in Illinois. Before he can kill Tommy's estranged son Austin Reynolds, he is captured by Sam and Crowley and Dean kills Cain with the First Blade.
Sam and Dean visit the Lizzie Borden Bed and Breakfast Museum, much to Dean's dismay due to his aversion to Sam's fetish for serial killers. Lizzie Borden was commited for hacking her father and stepmom with a hatchet in 1892. She ended up getting acquitted and spent the rest of her life persecuted by the townspeople.
Len Fletcher talks about how he and Amara were discussing Lizzie Borden. He stated that her uncle had stronger motive and opportunity to kill them, but Amara tells Len that she can tell that Lizzie definitely killed her victims.
Nick goes back to Pike Creek to visit his old neighbor Arty Nielson and ask him about the murders. Arty reported seeing someone leaving Nick's house at the time of the murders, but he later changed his story. Arty denies seeing anyone, but Nick soon becomes agitated and lashes out at Arty. He later beats him to death with a hammer, the modus operandi matching his family's deaths.
Sam shows off his knowledge of serial killers by mentioning Robert Leroy Anderson, who was a killer in South Dakota who was convicted and sentenced to death in 1999.
Nick visits a priest who Arty visited to receive confession. He wanted the priest to reveal what Arty told him about that night, but he was uncooperative as the nature of confession is confidential. Nick then slits his throat and nails him to the door frame.
After he finds out about Frank Kellogg, Nick heads over to Montauk to see him. On the way, he sees a young woman walking out into an alley from a club, and contemplates whether to leave his car, ultimately deciding to walk up to her. He takes out his knife and hides it behind his back. She invites Nick to come inside and party with her and her friends, but he tells her to leave.
Nick arrives at the home of Frank Kellogg and asks him about what happened to his family. Kellogg tries to slam the door on Nick, but Nick catches him and ties him to a chair. Nick tells Kellogg what Arty told him before he died: He saw a cop leaving Nick's house that night. Kellogg later reveals that he went to Nick's house to respond to a call made by Sarah about a possible prowler. Outside the house, he meets someone named Abraxas, but he doesn't remember anything else before he woke up in his car covered in blood. Nick recognizes the name and realizes that Lucifer knew that name. Nick realizes that Abraxas is a demon who possessed Kellogg and used his meatsuit to kill his family. When the cops discovered what happened, they covered up the murders to prevent Kellogg from going to prison. Although Nick acknowledges that Kellogg is innocent, the demon still used him to kill his family. He then proceeds to beat Kellogg to death with a hammer.