For some unknown reason, apropos of nothing, last night my husband said “Jimmy Stewart would have been a really bad actor to cast as The Godfather.” It is pretty funny to try to imagine. What are some other combinations of actors and roles that would not have worked at all?
Pauly Shore as Hanibal Lecter. (Although Pauly Shore as anyone is a miss in my book.)
I was thinking Pauly Shore before the thread even opened.
Don Knotts as Captain Kirk
Danny DeVito as Lurch
Rip Taylor as Frodo
Johnny Depp as Willy Wonka.
Oh, wait…
John Wayne as Genghis Khan. Oh crap…no…really?
Eliajah Wood as Malcom X
Keanu Reeves as Dr. Frank-N-Furter
The Govenator as Mother Teresa…what do I win ? 
Mo’Nique as Vern Troyer.
Or vice-versa.
John Wayne as Frank N Furter