When I first went to pick up Mutants & Masterminds, it had just gone into the Second Edition and had unexpectedly sold out - period. Green Ronin had to put out a second printing due to the success of the game. Needless to say, I managed to get a hold of a copy, and I have very much enjoyed the game.
What about the game have I enjoyed? First off, it is a d20 game, and as such, it has some familiarity of the d20 engine. However, it is very off from the rest of the d20 games like Dungeons & Dragons or d20 Modern. The game does not use hit points. It does not have classes or racial packages. Instead, you have 15 points per level to build your character with. The system is very flexible and is meant to be rather cinematic.
The game goes on to use the Feats system of the d20 system and expand upon them. Additionally, you have Powers, which can be adjusted with Extras & Limitations. There is a lot there, but once you have it all in front of you, it runs fairly smoothly.
The game is designed to be a superhero game, but it has a lot of flexibility. You can put together a four-color game, a western-style, suspense/horror or any number of things. Yeah, GURPS and Hero System did this a long time ago, but this version is not nearly as math intensive and allows for more cinematics, not letting the rules overpower the story.
On the other end of things, if you like a very visceral game, this is not the game for you. Yes, it can be violent, but it is not designed to be about killing orcs.
Overall, I really enjoy the game. I have both played and ran the system, and I plan to run more games in the future. Green Ronin produced a quality product that I would recommend to any gamer or comic-enthusiast looking at trying role-playing.