Man, I just thought of a whole plot for this and I wish I worked for Marvel.
Key plots:
Villains unite once more but this time achieve their goal of stopping the heroes. In some contrived way they imprison them or get rid of them so that they're out of the picture. These are the core heroes: Avengers, Fantastic Four, X-Men, etc. They didn't bother much with the younger nobodies. They deal with those on the side.
As they gain power and draw lines over the world/USA we begin seeing factions. There are those who crave power and absolute rule working together and dividing things among themselves. I imagine these being the likes of Sinister, Red Skull, Kang, Ultron, etc. The big names. I don't see a leader among them but a Round Table type of councel.
Other villains, however, were more interested in the money, respect, and vengeance. Now that they've attained their goal they're realizing just how messed up some of these bigger named villains are. They're the villains who, on occassion, might show a good side because they aren't all bad. I'd imagine they'd mostly be street-level villains who don't actually want to rule or kill the masses to get their way. I'd imagine the likes of: the Shocker, the Wrecking Crew, Daken, Doc Ock, etc. I can see the crime bosses organizing them, like Kingpin, Hood, and Hammerhead.
Eventually I can see a "hit" being made on one of the crimb bosses, Kingpin likely, but fail and this will launch the Villain Civil War. I can see the "hit" that was supposed to have been called in by the bigger villains actually be done by Daken, or some strategic member of Kingpin's side to kickstart the battle.
During the Villain Civil War I see the heroes who were overlooked, the young ones like the Young Avengers, the Runaways, the New X-Men, the Future Foundation, Avengers Academy, coming together and weaving their way into the war and secretly begin taking out key members of each side... maybe siding with the street level villains at first.
In the end the Villains do each other in with the young, overlooked heroes of the Marvel Universe being the ones to score the big win and getting their senior heroes back from wherever they were sent. Once the heroes are back the Villains will spread and order will be regained.
This would give the young heroes of the Marvel Universe a MUCH needed boost to make them relevant and would likely help them support new ongoings to advance the line and universe. There's always the worry that they can't support their own books and people would jump off if they took over a book, like when Daken took over Wolverine, but if it happens in the middle of a Villain Civil War I think the premise will help keep people reading. So the young heroes could take over the established heroes titles for this event alone.
Avengers Academy and the Future Foundation already have books but besides them:
Alpha could take over Spider-Man
Spider-Girl could take over Avenging Spider-Man
Skaar could take over Incredible Hulk
Lyra could take over Hulk
X-23 could take over Wolverine
Young Allies could take over the Fantastic Four
Young Masters could take over Dark Avengers
Young Avengers could take over the Avengers
Initiative kids could take over New Avengers
Cho, Power-Man, Thunderstrike, Spider-Girl could take over Defenders
Runaways could take over Astonishing X-Men
Utopia's New X-Men could take over Uncanny X-Men
Wolverine's New X-Men could take over Wolverine & the X-Men
Generation Hope could take over X-Men Legacy
You get the gist.