Arkea as a sapient bacterium that infects technology would be very easy to make an MU-wide threat. Start with her hijacking Iron Man's armors, merging with Ultron and his descendants, corrupting the Extremis viral formula, or even taking over the Phalanx or some combo of all the above to raise a kind of cyber-zombie army that ravages the Marvel Universe, Earthbound and more cosmic settings alike. Could actually put the symbiotes to shame.
Selene vs. Candra, who shall be the supreme reigning immortal mutant villainess? Battleground . . . the entire Marvel Universe, with Candra marshaling and expanding the Assassins' Guild, Selene raising a new death cult, as per Beetle's suggestion (I think she might be using her new position in Ta-Nehisi Coates's Captain America book to do that, anyway), to fight for her, and the heroes (and villains) of the MU caught in the middle.
Madelyne Pryor and Miss Sinister could team up to form a new Sisterhood, first taking out Mister Sinister and taking all his resources, particularly his stockpile of superhuman DNA from both mutants and nonmutants as seen in Hunt for Wolverine: The Adamantium Agenda, for their own ends.