I think it's hard to top Anthony Hopkins/Hannibal Lecter in Silence of the Lambs.
Others I'd mention
Sean Penn/Spicolli in Fast Times at Ridgemont High. Also from Fast Times, as a 12-13 year old boy, Phoebe Cates had a huge impact on me personally.
R Lee Ermey/Hartman in Full Metal Jacket
Randall Tex Cobb/Leonard Smalls in Raising Arizona
Keaton/Bettleguese in Beetlejuice (saw someone claiming he had less than 17 minutes of screen time)