My theories, cross-posted from a thread from 6 months ago...
Heroes:
We'll get Sky-Scraper and Captain Cosmic as our two heroes, with Guise relegated the following expansion (or perhaps a mini-expansion).
Sky-Scraper's deck will revolve around hand-size as is the case here. She won't have a damaging power; rather, her base power will be something like Draw two cards. She'll likely have another power in her deck which gives her a consistently damaging power. Most of her damage will revolve around one-shots, possibly with a rider that makes her discard cards (which would keep her size in check). A possible one-shot for her might be something like Deal one target X damage, where X equals half the number of cards in your hand. Discard 1 card. Another might deal damage to all non-hero targets (I picture Giganta in the final episode of Justice League Unlimited, sweeping parademons off of the Eiffel Tower), but with a higher discard cost. I still do like the idea of her being able to do a sort of "Final Dive" against Environment targets only, picking them up and throwing them at Villain targets.
I see Captain Cosmic as something of a combination of Green Lantern and Captain/Ms. Marvel, able to manipulate and redirect energy and create energy constructs. It'd be interesting to see him have a power (probably not a base power) that read something like Deal one target X Energy damage, where X is the amount of energy damage taken since the end of your last turn. More likely, he'll start off with a simple damaging base power like Deal one target 2 energy damage. With the former power, it'd be neat to have his one-shots and the like deal him a small amount of energy damage, which could stack up to be unleashed in a big blast. I could also see him having some degree of battlefield control, perhaps with an "Energy Bubble" which would function like Fanatic's "Chastise". It might read something like Choose one non-hero target. That target cannot deal damage and cannot be dealt damage until the start of your next turn. At the end of your turn, this card either deals Captain Cosmic 2 energy damage or is destroyed.". I could easily see Captain Cosmic creating a "Hard Light Cannon" that can then be used as a high-damage power, with the drawback of having hit points and being treated as a hero target, so that it could be destroyed both by Ongoing destruction and by taking damage. Plus, you could end up with a card that reads something like Destroy all of your Hard Light Constructs. Deal each non-hero target X damage, where X is twice the number of constructs you destroyed.
Villains:
Again, all of this is conjecture, but let's take a look at the comics tropes (particularly the space or cosmic themed ones) that don't already exist in the SotM universe.
I could easily see one of the villains as a take on The Brood from X-Men or Annihilus' swarm as seen in Annihilation: lots of swarming targets, perhaps which latch onto heroes a la Gloomweaver's voodoo pins, preventing the hero from dealing damage to anything but the attached 'bug'.
We don't have anything that really represents anything like Brainiac (DC) or The Collector (Marvel), so seeing a mashup of those two would be pretty neat. Omnitron's the closest right now, but even that doesn't quite fit the archetype. I'd see these playing as something akin to a combination of Omnitron with La Capitan, with a fair amount of equipment/ongoing 'theft', perhaps with a condition similar to Plague Rat's "Infection" cards, representing that hero being placed in the villain's menagerie.
If Captain Cosmic is true to the genre (being an inheritor of the Green Lanterns or Nova Corps), we could potentially see his nemesis as a group, rather than a single individual: something like the Weaponers of Qward or the Manhunters would make sense. Plus, it seems that the >G gang is more willing to provide villains in a "deck-style" format, considering the Vengeance villains and The Ennead. I'd be interested in seeing something like a Yellow Lantern Corps in a villainous context, working similar to The Ennead's deck, though without the reliance on the Sun/Ankh/Hand symbols.
We already have a "space tyrant" in the form of Voss (owing echoes to Darkseid, Thanos, and Mongul), but perhaps we could see something on the level of an intergalactic "peacekeeper" in the vein of Ronan the Accuser or Adam Warlock, or even an homage to someone like Granny Goodness? I'd see his deck playing out more like Iron Legacy's or Ambuscade's, perhaps with a handful of villain targets to accompany them.
Environments:
One I'd really love to see? Something like DC's War World or Marvel's Battleworld (from Secret Wars)--a great arena where heroes and villains show down for a cheering crowd, coupled with alien beasts thrown in to even the measure. One neat card for this sort of environment would represent the crowd's approval: if you deal more than 5 damage in a given round, perhaps you regain a hit point or deal +1 damage until the end of your next turn.
Alternatively, the crossfire of an interstellar battle might go well, particularly if it were between Voss's invasion forces and a fleet of defending ships. I see this one being somewhat similar to The Block, in that you'd have two opposing forces going at one another, with the Heroes and Villains taking damage from both.
If the second doesn't happen, exploring the ruined remains of a space station or capitol ship could be a lot of fun. I'd worry about the similarities to the Mobile Defense Platform, but I still think there's room for some great differences, especially if the creatures that took down the ship/station were still lurking aboard!