It plays great solo using two hands, but I'm not entirely sure it scales well for 2 players. I haven't come close to winning yet, and I think it might be a little easier to win with 3-4 people being able to attack together (with the additional power points not being that big of a deal). Just my theory, though. And it's really fun, regardless.
Lisa and I have been playing against each enemy playing both a 2 player game and a virtual 4 player game by playing two players each. We first thought that we were going to prefer two players each with all the cards that interact with your teammates, but we're finding both player counts fun and playable.
Playing just 2 players, you get some nice breaks to build up while the monsters accumulate power - this can be very handy! But, if they start getting power boosts coming out, things can get nasty very quickly since it's a much greater increase in their power generation than it would be in a 4 player game.
It's been quite easy to play 2 players as soon as we got into the habit of just spreading our hand of cards on the table.