Wesley (William Lee Scott), a guitar player and convicted car thief, is sent to live in a halfway house whose inhabitants are required to play hymns at the nearby Christian college. None of the convicts want to be in the band, and their music is half-hearted and insipid, until Wesley persuades autistic savant Vernon (Lucas Black) to join as their new pianist. Vernon brings out his bandmates' hidden talent, and together he and Wesley transform the group into a rocking blues band, the Killer Diller Blues Band.
Killer Diller contains examples of:
- Air Guitar: While the band is playing at a school, Wesley sees Vernon playing air piano on a table. Exasperated by his bandmates' apparent lack of talent, Wesley wanders over and starts air guitaring next to him.
- And Starring: Taj Mahal as "J. R. Cox" introducing Niki J. Crawford with John Michael Higgins and Fred Willard.
- The Cameo: Taj Mahal appears briefly as Wesley's dead mentor.
- Chubby Chaser: The two women in the halfway house are both attracted to the men at the fat camp across the street.
- Fantasy-Forbidding Father: Vernon's dad bans him from playing with other people, so Vernon has to forge his signature on the permission form and sneak out to performances.
- Friendless Background: Wesley grew up in an orphanage, and the one person he was close to is dead. Vernon's father overprotected him to the point where it would have been hard for him to make friends even if he'd been neurotypical.
- Middle Name Basis: Vernon's full name is Jules Vernon Jackson.
- Missing Mom: Vernon's mother is dead. Wesley tells people that his is, too, but the truth is that she walked out on him.
- Potty Failure: During Vernon's first public performance with the band, he wets his pants after one song. Ned, who runs the halfway house, likes Vernon's playing so much that he lends him his pants so he can continue.
- Reformed Criminal: Most of the main cast.
- Talent Double: Tree Adams on guitar and Jeff Babko on piano.
- Workout Fanservice: Vernon's out-of-shape dad likes to watch workout videos of sweaty, muscular women.