I've ran a Super Villian campaign before. (Though not using the M&M system)
There are some simple things you can do where you don't have to have the players follow any sort of rules.
1. Money Money Money Monnnney!
You can't have HQ, equipment, doomsday devices, etc without it.
I'd first institue a wealth system. But don't sweat it if they try to circumvent you with the "I'm rich!" thing. Make sure they explain how their rich. We'll get to how you'll deal with it soon enough.
2. The primary driving force for nearly all PC villians will fall into one of these four catagories:
Dominance (be it World, City or Otherwise)
Power (but if it's to exert it over others it becomes dominance)
Wealth (even if it's to support dominance or power)
Meaness (some villians are mean, just to be mean)
Once you figure out which one(s) your players are driven by it becomes easier to manipulate...I mean GM them.
3. Consequences. Here's the main difference for your villian campaign. What happens when in a Hero campaign the heroes lost the fight? Generally not much, they lick their wounds maybe mourn for a fallen combatant. Villians, however, if they lose they go to prison or some such. Of course you don't have to RP the prison, in fact you can even start the next mission under the assumption they escaped.
However, in my campaign, if the villian was ever caught by Heroes..they lose everything. Headquarters, gone. Bank accounts, gone. Minions, gone, sometimes. Cool devices, gone. The newfangled "Lay-Zer" you ordered from ACME...gone.
Basically the villian has to start from scratch with his possessions.
Most cheap "thug" hinchmen would've split when the authorities started seiging the "secret" hideout.
If they were independantly wealthy, theres a chance being on the authortie's radar like you were when captured let to them discovering your funds and seizing them.
This perpetuates their need for money. And makes them a little more cautious. In terms of keeping them from going too crazy with their evilness.
The misconception your "would be" villians will make at the begining is thinking that since their evil they have nothing to fear. That they have nothing controlling them. This is partially true, they won't have the moral or legal boundaries like heroes. But they do have something controlling them, Money!
Anyway's I'll stop rambling cause I don't know if any of this is helping you or not.
But running a Villian campaign can be a blast, and hilarious.
"Hey Demonlord, I thought you were going out today to lure some newbie hero into a deathtrap....and why are you peaking through the corner of the window?"
"Shhhh....that nosey old lady who lives across from this abandoned warehouse keeps staring over here... I'm having trouble sneaking out."
"Um...why don't you just kill her?"
"Because stupid, I don't know if she has family who would miss her. We don't need the Pigs snooping around here, do you realize how hard it is to find an abandoned warehouse in such a centralized location???"
Also play off a few things unique to villians, such as:
Minions no matter how loyal are dumb. If they were smart they'd be Villians. They're always accidently telling secrets, leading heroes to the lair, messing up the equipment...etc.
There's almost always that one hinchmen or underling who wants to be leader, and will do all he can to sabotoge your plans to make you look uncredible, but without the brains to pull it off correctly. Without you finding out of course.
Villians are always having turf wars with other villians, but they also have to avoid the cops/heroes in the process.
Also, this isn't nessessary, but our campaign started at low level (the PCs were trying to make a name for themselves...having to work as hinchmen themselves at times) and they would work their way up to try to show themselves as real super-villian contenders. Think GTA3 with powers.
I had it just as easy though making missions for them as powerful as when they were low-level.
It's actually really hard to be an effective villian...you have to deal with so much more than heroes, and to top it all off you never know who you can trust.
Weak in Search Fu 
