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Over the course of One Piece, death has not really been a huge factor. That is until Ace and Whitebeard's death in Marineford. It makes me wonder if there is going to be more deaths in the future. Here's my predictions...
Shanks - I think that when Luffy finally manages to find Shanks, the Straw Hats and Red-Haired Pirates are going to fight against each other. It will be an extremely tough battle but the Straw Hats will come out victorious, fulfilling part of Luffy's dream to have a pirate crew that surpasses Shanks. Obviously there is going to be a huge celebration with both pirate crews but then Blackbead is going to show looking for both Shanks and Luffy's head. Shanks and his crew (who is extremely weaken from their fights against the Straw Hats) will sacrifice themselves to allow the Straw Hats escape.
Doflamingo - Because of his connection to Kaido I believe he will die because of 2 reasons. 1) Kaido is known to be an extremely ruthless person who, if he wants to, will kill anyone he wants, like any pirate but he has the power and influence to hunt you down and kill you. 2) Luffy will beat Doflamingo but like we all know he doesn't kill, so Doflamingo will escape but because of his deal with Kaido going sour, Kaido will hunt him down.
Marshall D. Teach - Better known as Blackbeard. Obviously his crew and the Straw Hats are going to have a showdown near the ending of One Piece. However, like I said before, Luffy doesn't kill so I believe Blackbeard will just get beaten to a pulp like the other characters Luffy has fought against and Blackbeard will be captured by the Marines. Because Fleet Admiral Sakazuki will not be so merciful as Sengoku, he will immediately want to execute Blackbeard and because he is weakened by his fight from Luffy he will get captured and executed.
Please I would love to hear any other predictions on whoever else you may think will die and how their ends will come.