I had the same big bad throughout my 2nd and 3rd Edition campaigns. I had used a lot of protagonists but the one lurking in the background up until the end was a Seoulpa Ring run by an Ork Ant Shaman. They introduced a new drug on the market and financed and up and coming street gang. His main motivation was to funnel money and arms to resistance movements in San Fran against the Imperial Japanese Occupation forces. Once he had the queen, they also went after Ares as well. They created a method of almost guarantying a good merge and went about replacing beaurocrats, corp suits, and mafia made men while moving towards their slowly divergent goals. Eventually I ran a game that had the runners uncovering a plot to smuggle Soviet era nukes into Detroit and San Fran. I ended my 3rd ed campaign with a run to capture the Queen for a dragon that ran an R&D lab for Ares. After the loss of his Queen, the Shaman, who was already old for an Ork, died of heart disease, a blessing for the runners.
In 4th Ed campaign, I had a master Shedim partner up with a militarized wing of Gao Fong in Hong Kong that culminated with an Astral Rift being created and lots of chaos. I then went through the Emergence plot line and had MCT as the big bad, who in a twist of fate, the PC's had to save a bunch of MCT Sararimen and their nemesis from a very unstable and powerful technomancer they thought was an ally.
I also love the idea of shadowy groups far behind the scenes, and I have had one that I have used since 2nd Edition and still use to this day. I LOVED Earthdawn, so I had to take one of their big bads and keep them in the 6th World. I have a modern version of the Cult of the Great Hunter filled with the rich and shadowy. My current favorite member is a Cantonese Blue Blood with no magical ability but has been a part of the Cult since he was inducted in his youth. I use them as a mirror to show the worst reflections of society. They eschew love for carnal pleasure, seek power for the sake of power, disregard compassion for weakness and are driven solely by their own desires. Awesome fun times!
