Maybe they will attempt to discredit the religious artifacts that showed up in the previous two films, by saying that the Ark of the Covenant and its power were not from God but from aliens, and the healing power of the Holy Grail was simply more alien technology. That is why they are in the warehouse searching for the Ark, so they can use it for clues to find the alien colonies on earth from which these "magical" artifacts came from. Perhaps this film will provide a sci-fi rationalization of the supernatural events of the previous three films. But I am pretty sure this is nowhere near, I honestly can't believe it would sink that far. Perhaps if George had complete creative control, but as it is he has plenty of people to keep him in check. I just hope in the future I will be able to admit to liking the Indiana Jones movies without being snickered at. Anybody else remember the days when you could tell somebody that Star Wars is a cool movie without having them roll their eyes at you?
EDIT: Pretty sure that "speculations or major spoilers?" link RRS posted is completely made up.