Just to push back a little, last night I watched a three person game, in which an experienced player choose Robots and Zombies. She did not win, though it was close.
I also played a 3 person game, choosing Zombies and Pirates. Though it was my first time, I did pull ahead a good deal and won by ~4 points. I think that Zombies are well suited to new players and when complemented with minion-heavy deck, since they are all about pulling minions out of discard. I would recommend not pairing the two action-heavy decks (Spellcaster + Trickster), but otherwise I felt most combinations had real potential. It might be too early to say for sure though. If Zombies turn out to be overpowered, I might just take them out, or institute a house rule that minions played from the discard do not get their text activated.
I think it could fill a niche as a simpler, quicker Bloodbowl:TM. Though King of Tokyo might be preferable in most situations. My main complaint with Smash-Up was how so many creatures and bases had special powers. It makes for a lot of reading and remembering, but for $20 (@ CSI) I'll be happy to try it more when it's released.