Game of Thrones
Game of Thrones was a show famous for its high number of characters, so it made it all the more confusing when Sir Beric Dondarrion was replaced out of nowhere. David Michael Scott played the role for only one episode before being recast by Richard Dormer. Amazingly though, that wasn't Scott's only day on set. He returned to play Beric's brother in a later season. It was very confusing for those with a great memory.
Back to the Future
I bet this actress wishes she could go back to the future. Elizabeth Shue replaced Claudia Wells as the girlfriend of protagonist Marty Mcfly. After filming the first movie, Claudia's mother became very sick and was diagnosed with cancer. She had to leave the production of the second film, as well as her entire acting career, to care for her mother. The job couldn't wait that long, so Shue took on the role.