Avengers: Infinity War - 12 Plot Twists No One Will See Coming
12. Spider-Man Dies
Well, at least temporarily...
The footage shown of Infinity War at Comic Con included an emotionally loaded exchange between Spider-Man and Tony Stark, with the former apparently gravely injured apologising to his mentor.
While most would dismiss this as mere artful manipulation in the footage, it actually does make a lot of sense that Spider-Man would be one of Thanos' highest profile victims. His arc is essentially following the Civil War storyline that sees him become Tony Stark's pro-registration poster boy who unmasks and unwittingly puts his family in grave danger as a result.
The specifics of the story may be different, but the story trajectory is there. Instead of unmasking being his big mistake, joining up with the Avengers prematurely would be, and he would be the true, devastating cost of Tony Stark's reckless idiocy. That would also explain why Spider-Man is said not to have a huge part in Infinity War - because he's killed off.
There's no way the death would last of course, and it's fairly certain that Thanos' actions will be reversed (just as they were in the comics), but killing Spidey even temporarily would be a great way to underline the Mad Titan's threat, as well as side-swiping the audience.