Considering how She-Hulk #15 is supposed to be taking place after Civil War, I go out on a limb and suggest that the "New" S.H.I.E.L.D. director (unless Marvel is STILL calling Maria Hill that) is going to be Nick Fury, who is offered his old job back after bad PR from her mishandling of the Secret Avengers, the New Thunderbolts going out of control and the Atlantis Invasion demonstrated her "lack of experience" and her "incompetance" and they need a "seasoned pro." It would also indicate that while superhero registration is still the law of the land, Iron Man side will technically lose because his action have worsened the situation, not less, meaning that Iron Man's team of Avengers are "relocated" to another state so he won't be such a figurehead (it would also mean Cap will probably be heading a Avengers team under Fury's supervision).
And it looks like with Black Panther and Storm coming to Cap's aid, it seems the idea of them leading a new Fantastic Four may not be so far fetched, considering how I think Reed is not going to come out of Civil War all that well and probably be imprisioned, especially if he had anything to do with monkeying around with the Thunderbolts nanocites. Oh, and it's not so shocking that Tigra might have gone over to the anti-regs. She did question Stark about whether Cap's bunch was regarded as Tony's group of unfit heroes back in Civil War #2, so Golitah's death may have solidified her feelings that Iron Man's bunch is far more dangerous than the supers they're apprehending.
As for the Return, I believe that 42 is actually the designation of the hero who is trapped in the Negative Zone and not an actual place. And considering the cover, I'm guessing that it will be Captain Marvel, or rather his clone. Considering Reed's dabbling with the Thor clone, I imagine that it will be revealed that he also cloned Mar-Vell right after he died, but placed him in the negative zone because he was either too "independent" or not fully developed.