There are multiple valid answers to that. Magus was the one who got the Sirleck/Vampire balls rolling, so he could be considered the primary antagonist of that plot-line (or the protagonist, by the older definition where they were the one who caused changes and drove the plot), even if he wasn't even close to 100% evil and got away in the end. Meanwhile, Voltaire manipulated Sirleck (and in so doing orchestrated Pandora's reset) and was trying to influence the outcome of the Magic change, so he's also a good candidate for the primary "villain" of Sister III.
The Old Hack's view that the primary obstacle was the change in magic itself also holds some merit.
...Actually, though, this doesn't really feel like the end of an era to me. Sure, it's a major turning point, but Pandora will be back, the masquerade isn't going to be dropped immediately, and the change in magic didn't result in anyone loosing any magic. Pretty much the only things that ended were Pandora's instability, Magus' time as an incorporeal entity, and Sirleck's life, none of which I expect to have a major impact on the main cast's lives (at least once they get past the worst of the pain of Pandora's reset and until Magus launches his next plot, whatever that might be). The magic clog is supposed to end too, and that might actually have a big impact on the cast, but we haven't seen that yet.
I think what will really serve as the biggest ends-of-eras in EGS will be the cast getting out of High School, and (assuming the comic gets that far) their getting out of College. I suppose it would be quite the coincidence to have the gang have to deal with Lord Tedd right around one of those times, but that's the sort of thing I was thinking of.
And a love triangle.