Since the special ending after the credits of Tales of Monkey Island, I think it would be cool if Elaine became the main character in the next game. Morgan would make an interesting villain since she's in love with Guybrush and would probably stop at nothing to get him.
With Elaine as the new protagonist, players could see the game in her perspective as she gets a taste of what Guybrush does. Or Elaine and Guybrush could be switchable characters allowing for puzzles to be multi-layered and have more complex solutions. (Kind of like the beginning of Tales Chap 1 when Elaine uses the rope to let Guybrush across the mast to get to the other side of the ship.)