Probably the most satisfying campaigns I've had to run and participate in were on the old X-Men Movieverse: X-Factor game, where the core of the game was as secret mutant government agents. Since plot required missions required GMing, there was often times where we had back to back plots from staff and players. We had a big shadowy organization that was our rival to dismantle over the years. Since things were secret agent mission-based, we weren't as reliant on single players to carry things through; we could shift plot around a little easier. When I started on staff, I was unemployed and pretty sad about it. Never have I had more time energy to help run plot and more investment in a game, and now that it's years later I know I never will again. Unfortunately, that level of plotting is a total staff burn-out, which is what eventually happened. I'm still really sad we couldn't wrap things up better.
When we decided to close Mass Effect: Alpha & Omega, we specifically planned it out several months in advance to out with as satisfying a bang as possible. I really liked that we got to go out as epically as possible for that one.