Well, when I run games, it doesn't matter what the system is. The PC's don't need enemies. They have each other!
Seriously, though, in one of my games, the big bad is the conflict between the Coalition and the Federation of Magic, and the heroes are caught in the middle. The GMPC is the magical granddaughter of the affair between Joseph Prosek and a mysterious magician.
In another of my games, the villain is a family of Clan Aeheriman whose wayward daughter chose the path of the Cyberknight, and they're desperately trying to hush it up because it's an embarassment to their superiors. Of course, forty Sunaj is a pretty tough group of people, but you know, they really shouldn't be fighting them all at once. (The oath of non-interference says you can't openly TELL anyone about the Sunaj. The oath does NOT say that you cannot SHOW other people by proxy if you share a common enemy with them.
)
In another of my games, the villain is a C'ro Demon Mage who's taken up Residence in the New West. Well aware of psynetics and the large Brodkill population, he's cut a deal with the Angel of Death halfway across the world, and is busy testing things for her while building an army of Brodkil, Monster Brodkil, and Crazies to crush the Barony of Hope and Silvereno beneath his stingery heel. Sadly, this guy's not friendly, and has his very own Naruni Sun Chariot Power Armor. Nothing like blowing up a suit of power armor to discover a Cro Demon Mage underneath!
In still yet another, the current enemy of the PC's is Guktar Tagos, an Ogre Mind Melter. With his small group of hired juicers, after being defeated by the PC's and arrested, currently he seeks to acquire the bounty that will presently arrive on their heads. Sentenced to death, he modified the memories of his firing squad with his hired Delphi Juicer, and now everyone believes he's dead. Unfortunately for them, he's alive and kicking. (See favorite moments in Rifts on another thread for information about this bounty.)
So who's my favorite villain? The secret Banking Consortium of Robert Holcroft, Assistant Director of the First Bank of the Coalition, Gazmir Thraztikkar, an influential Great Horned Dragon in the GDSL, and Skeebo Runthrait, an assistant to the Naruni Banking Consortium. Together, these three gentlemen manipulate everything that goes on, from the price of weapons to the very existence of the JA-12. Using the JA-12 as a profit base, plus the profit from juicer conversions, they use this money to move and manipulate vast sums of cash, alter the course of wars, and make the three of them all filthy stinking rich without the knowledge of their respective banking organizations.
Talk about a bunch of bad guys.