No one stays dead. Now, I'm not complaining about the unrealistic aspects in a story that involves people getting superpowers from cosmic rays. What bothers me is that it sucks most of the drama out of these ultra-dramatic moments, so then, really, what do you have left? An exception to this rule is Civil War: The Confession by Brian Michael Bendis, one off the finest single-issues ever written.
Too much promotion. Marvel has been promising in ads that someone will die. Although the title Three pretty heavily foreshadows death, a number of outcomes are possible (maybe Ben Grimm quits to join the Avengers full-time). Anyway, it kills any surprise that might be waiting. An exception is the end of Thanos Imperative where (Spoiler Alert) when Nova and Star Lord go out blazing like Butch and Sundance. This wasn't advertised at all, and it's believable because, honestly, it's conceivable that these two characters can never make an appearance again.
Death Sells. I never understood this. Every time, a superhero death boosts sale. Why? I mean, I understand that some chump sees that Batman is dying on the TV, so he'll run to a store and buy it thinking he'll be able to sell it for a lot of money one day, but why do comic book readers who know the character will return in a year. I mean, I'll buy it, but that's because I've been buying Fantastic Four every month for the past year and a half. I didn't buy the Captain America death issue, because I wasn't buying Captain America. When dealing with an A-list character, there is never an exception.
Predictions:
2 to 1: Reed dies. If anyone has been reading Hickman's run (or last month's issue), this is the obvious choice. Not in a bad way, but structurally, this is where the story is leading to. Almost anything else would be bad writing for shock value.
10 to 1: Ben dies. This was a little more plausible a couple months before Marvel started using him in 2011 ads. Anyway, Ben's turning human in the beginning of this arc cannot be a coincidence. It would be tragic if this caused his death. In light of the aforementioned ads, I now think it would be tragic if Reed dies because a depowered Ben can't stop the threats or save Reed.
50 to 1: Sue or Johnny dies. I don't see how this would fit the story.
100 to 1: Someone else dies. Marvel claims its a team member, but you never know with these things. It could be misdirection. However, with all this publicity, it seems that could cause some backlash.
Bonus Prediction: We know that after Fantastic Four ends next month, Marvel is relaunching it as FF at issue 1 in March. My prediction is whichever character dies will be brought back in a year, so that Marvel can change the numbering back to 600.
