John Wayne was the victim in probably the worst casting decision in Hollywood history, when he was selected to play none other than Genghis Khan in The Conqueror. The gaffe was compounded by Susan Hayward as a red-haired Mongol princess.
The following year, Jimmy Stewart was involved in what could have been a similar disaster, when the 48 year old Stewart portrayed a man half his age, Charles Lindbergh, in The Spirit of Saint Louis. Stewart though actually pulled it off. He had the benefit of knowing the real Lindbergh, who was only 6 years older in real life.