Don't be intimidated by the high number on High Roller's villain card: he doesn't start out with nearly that much HP.

Legacy normally fits nicely into just about any team, but combining his damage boosters with Tripwire or Sirocco's self-damaging effects is asking for trouble.

On the other hand, combining Next Evolution with Lead From the Front to negate all incoming projectile damage will make Tombstone and his posse absolutely miserable.

That's all I got for now.

Lao Feng: keep Judgment moving as much as possible in order to maximize damage to enemies and help allies.

Kain's main Power can keep Gloomweaver's Cultists from rising again as Zombies by sending all the Zombie cards back to his deck instead.

Hexterminator: Bringing along someone who can mitigate all the toxic damage you'll be receiving (Like Legacy's Lead FTF/Next Evo combo) definitely helps. Once Hex flips you might find it easier to win by helping him defeat all the rat people.

Blockbuster: Bring along some good healers, you're in for a long one. A smaller team might be more to your advantage. Be sure to include one or more heroes who can destroy villain ongoing cards, or Creative Control will make you miserable. Save a chuckle for his defeat screen.