OK, I'll make a first pass at explaining what the game is like and then I'll try to focus on anything that anyone would like to more about.
You have a board with a map of New York City. It
is rather... dry. However, it performs its function and to add much more to it would really just complicate things. The board/map's primary function is to show where there's trouble (robbery in Queens!, demon spotted in the Bronx!) and where the various heroes are who are trying to deal with it.
'Trouble' takes many forms, but primarily it tells you how high the Trouble level is there and how many VP you'll be awarded for taking care of it. Trouble also comes in various types and various heroes are better at dealing with different types of trouble (Reed's better when science is involved, Dr Strange is better when magic is involved). When you try to deal with Trouble, the level tells you how many dice to roll and after doing so you get your actual Trouble level which is then modified by things like Reed with science, etc. Let me back up one second. Each player in the game plays a team of four heroes and the mastermind villain of another player (and they all have very nice miniatures!). OK, so back to Trouble... after determining the actual Trouble level, the active villain player spends those points to pay for Villain cards to attack the hero(s) dealing with the Trouble. Maybe I spend 3 pts to bring out Venom and 2 pts to put Innocent Bystanders out. Battle commences and the heroes either walk away successful with some VP or they get a one-way ticket to their medical facilities.
Some headlines are designated as Mastermind headlines. These allow the villain player to do extra nasty things when buying Villain cards AND they can actually get themselves involved after the Trouble is dealt with. So in the previous example, right after dealing with Venom, you have to fight Dr Doom himself! When the heroes succeed against the Mastermind villain, they get to choose one of their team power-ups to use for the rest of the game (things like a Fantasticar). If they fail, the Mastermind gets one of his Master Plan cards which are essentially villain power-ups.
I've mentioned Villain cards, but there are also Resource cards. There are a number of nifty helpful cards in there, but mainly you'll get Allies. These represent temporary team-ups. For example, maybe you'll draw She-Hulk and you can pay for her to hang out with you for a while. The primary method of getting Resource cards is to take a Story action which also adds story events into the game like "Gyrich takes away SHIELD backing from the Avengers". These also can cause minor VP gain so sometimes you'll be hesitant to go get more Resource cards when you can see that you'll help another team's story and give them VP.
All of this doesn't come without cost and this is where the heart of the game lies. At the beginning of a turn you'll earn Plot Points. These points are then used to activate your team members and recruit Allies. For example, I might get 4 Plot Points on a turn. Then, I pay two points to ready Daredevil and Elektra, another point to put Dr Strange in a supporting position, and one more to recruit Black Cat temporarily. I don't have enough points to use Spider-Man this turn so he's stuck on the sidelines. It's important to plan out who you really need for the turn and it's important to find ways to gain extra plot points for use in the future. The way the game is designed, you'll likely have your smaller guys running around at first and then in later turns you'll be bringing out Thor to get things done.
I don't want to get into what a supporting hero is too much, but suffice it to say it means the hero can help the ready heroes. Also, many character have good support powers you'll want to use. For example, Reed's support has him doing research and it will essentially let you draw 3 Resource cards... which is very nice.
So who's in the game?
Marvel Knights : Spider-Man, Daredevil, Elektra, Dr Strange : Kingpin
Fantastic Four : Reed, Sue, Thing, Torch : Doom
Avengers : Cap, Thor, Iron Man, Hulk : Red Skull
X-Men : Cyclops, Jean, Storm, Wolverine : Magneto
And how do you win? Depends on the scenario you're playing, The basic scenario is Born Again and it's the first team to get to 15 VP, but there are about a dozen others like Inferno, Onslaught, House of M, The Coming of Galactus, Evolutionary War, etc.
OK, so I haven't talked about combat at all. Well I'm tired of typing!

I'll do that later, but for now you can digest this and ask any questions which might come to mind.