The most gaping plot-hole - or more charitably, the most pressing unanswered question in The Predator is one of motivation. We know that the "normal" Predator comes to Earth to help humanity against his "bosses" (who refer to him as "the traitor") but there is no hint of why. Was he suddenly just overcome with altruism? Was there something humanity did for him that made him realise we're worth saving? The idea that this killing machine would just suddenly go pacificist is a little odd.
On top of explaining why the Predator went rogue, it would also be nice to have some sort of clue as to why it's behaviour changed so dramatically at the start of the movie. In the first act, it was supposedly coming to be Earth's saviour and yet it was still killing people without prejudice and with extreme malice.
But then when it saw Olivia Munn naked, it decided she was to be spared and that it couldn't kill anyone she was shielding. There is absolutely no hint as to why it chooses her specifically, so there has to be SOMETHING to it (perhaps it was her family's DNA that was spliced into it in the first place?) Either way, a sequel would have to deal with it somehow.