Dean drives a 1967 Chevy Impala in Supernatural. It has significance because throughout Sam and Dean's childhood they, for the most part, didn't have a stable home while traveling cross country with their dad but they always had "baby" as Dean lovingly nicknamed her. She was there through everything with them.
After nearly getting caught by the feds and Victor Henriksen in 2X12: Nightshifter After escaping prison in 2.19: Folsom Prison Blues, the boys loose the original Kansas plates in favor of Ohio ones because they know the cops and FBI are after them.