As a newcomer to the system, the universe I'm setting up is derived primarily from the MMO, with the 6E books filling in the gaps. Some of my interpretations are based on misinterpretations, or on material I don't fully remember, but they seemed worth running with. Here are some key points:
Millennium City's technology has spread across the nation. However, the population of the city itself has dwindled between repeated attacks by Tacophanes (He didn't actually use zombie heroes every year, but he did attack every October, and at other predictable times) and the revelation of Quiplothic radiation buildup contributing to an evacuation of large areas of the city. Primus and allied hero volunteers are working to clean that up.
Luther Black forgot his original plan for 2012 because of his dark magic warping his mind, leading to the simpler and more self-centered plan seen in the MMO. He is now gone permanently, but factors have allowed DEMON to continue without him - even without a new master plan.
The Demons summoned by DEMON (at least, some of them) are Quiplothic horrors forced to disguise themselves as hellspawn. Luther Black forced them to in order to keep up the illusion that he was just a Devil-worshipper. They're very annoyed by this (in their alien way), and most of them dropped the charade as soon as he was gone. Others have kept it up because the Demon shapes have advantages, and they can't put the disguise back on by themselves.
Cases of Vampirism and Lycanthropy are on the rise, but so are new and better cures for the conditions. While magical in origin, the curses have begun to mutate like conventional diseases, leading to variations - some more dangerous, some with different weaknesses, and some with less of a corrupting influence.
The odd effect that prevented the general population from acknowledging the existence of magic seems to be weakening. In fact, it's the other way around: humanity is evolving (hollywood-style) to become resistant to it. Heroic factions who saw the blinders as a good thing have ruefully acknowledged that this has real benefits for humanity's future survival - with all of the supernatural threats that the average citizen could avoid better if they knew to be wary.
^On the other hand, that is why DEMON is experiencing a resurgence: with an influx of newly-aware and unscrupulous new recruits joining to learn Thamaturgy, and surviving veterans all too willing to teach it. Even if some of them go solo or defect afterwards, it puts the organization on the map again.
Shadow Destroyer was eventually defeated for good, and the fact that he existed as a separate person from the original Doctor Destroyer is no longer hidden. However, while this information is publicly available, it is not widely understood.
Back on the scientific side, ARGENT has officially been declared a terrorist organization with the same legal standing as VIPER. Contributing factors for this included low ranking personnel openly taking potshots at rookie heroes in public areas, being caught committing crimes, information about their secret projects leaking to government organizations and the press, and a certain large business owner who survived ARGENT's attempt to feed him to dinosaurs when he wouldn't agree to a merger devoting all of his resources to hindering them on the legal field. Still, even on the run from the law at every turn, they have continued creating new technology to use and sell on the black market. Laser weapons and body armor with origins in ARGENT labs have spread far.
Something happened in another dimension that set Istvatha V’han's plans for conquering earth back for years. This left her pawns already stationed on Earth out to dry, but they're still around.
The Commander leading the Gadroon invasion force is considering terraforming one of Jupiter's moons instead. It's looking a lot simpler.
The Millennium City Westside gangs, after severe setbacks, are trying their luck in other cities. Kevin Poe is in prison more often than not, but the Neo New Purple Gang has found ways to work around that. The Cobra Lords have developed a rivalry with the Dogz. The Maniacs and Black Aces aren't doing nearly as well, being based around ideals of teenage rebellion which their members are outgrowing. The Cult of the Red Banner always had a wider range and is still active, developing a rivalry with DEMON.
PSI is trying to think up new names to use for their front organizations (and so am I).