Dean: Why Lawrence?
Chuck: I don't know. It all has to end where it started, I guess.
Lawrence, Kansas is the hometown of the Winchesters. According to their police records, both Dean and Sam were born in Lawrence. The Winchesters left Lawrence shortly after their mother, Mary's death (apparently for New MexicoBoM, p. 41).
Other Lawrence residents included:
Lawrence is visited in 1.01 Pilot, 1.09 Home, 2.20 What Is and What Should Never Be, 4.03 In the Beginning, 5.22 Swan Song and 12.09 First Blood. 2.04 Children Shouldn't Play with Dead Things, has been considered by fans to be set there because Mary's grave is visited, but the Devil's Road Map from the Season 2 DVD indicates that episode occurred in Greenville, Illinois.S2DVD
During one of the voiceovers reading from Chuck's "Swan Song" manuscript, he says that Sam and Dean would go to Jayhawks games. The main campus of the University of Kansas is in Lawrence. The Kansas Jayhawks are the mascot/team name for all of the school's athletic teams.
Lawrence and its Ghost Stories
Lawrence and its surroundings have a couple of urban legends that are notable, e.g. the Stull Cemetery, which might just be a gate to hell. The graveyard has a church that has been abandoned since 1922 - it is said that rain won't fall over the roofless remains of the church, and an upside-down hanging crucifix will turn upside down when someone nears. BoM
Eric Kripke said in more than one interview that he chose Lawrence, Kansas on purpose, because of a very famous urban legend which originates there. Arguably, he means the Lawrence Stull Cemetery "Gate to Hell". The Stull Cemetery was set to be the location for Armageddon - the final showdown between Michael and Lucifer in 5.22 Swan Song.
In Lawrence itself there's a haunted hotel called The Eldridge Hotel - apparently, the fifth floor is haunted best. (The hotel's cornerstone was salvaged from burning ruins after Lawrence was destroyed by the Quantrill's Raiders in the Civil War.)BoM (Further Reading.)
The Haskell Indian Nations University is haunted by the spirits of Indian children who died there over the years due to the cruelty of the teachers.BoM