Dawson Casting: Most blatantly with Olivia Newton-John and Stockard Channing. By the time the film came out, Channing was 34 (and actually old enough to have been in high school in 1959) and Newton-John was pushing 30.
What Could Have Been: Steven Krantz and Ralph Bakshi originally had the rights to the film adaptation to Grease, and had wanted to do it as an animated musical. When Krantz and Bakshi's partnership fell through, Allan Carr acquired the film rights.
Harry Reems was originally considered for Couch Calhoun, but didn't get the part as Paramount executives feared controversy from casting a porn star in the film.