I'm running two campaigns right now, one in Planescape and another in my own homebrew world.
The Planescape campaign is a simple "things aren't what they seem" theme. And I don't mean tired twists of betrayal. Instead, most of the monsters I put out for them to combat seem weak, but are actually ingenious planners that give the party a run for their money. Such as when my party got their first quest. It was a simple go-to-the-abandoned-building-and-clear-it-of-rats quest. The problem was that the rats were cranium rats.

Poor adventurers... they got so complacent after those first few kills. Then the switches for the exits began to be closed by the uber-intelligent rat swarm. They never wanted to fight rats again after that.
My other campaign is being run here, and is called Last of the Dorinthians. Instead of the typical, save-the-kingdom theme, the party starts out as refugees fleeing the invasion of their country. So instead of saving the kingdom, they have to seek out a home for their people so that they don't become extinct. The theme to this is "Good and Evil Actions Under Desperation". It's partly political, with the players' actions determining how the other races treat the new refugees that lie on their border. Also, both PCs and NPCs have a lot of pressure to save their own people from enemies on the border. This gives the PCs a chance to justify their alignments and perhaps save other NPCs from falling from grace. I try to make it easy to make an evil decision, although that is rarely the best solution in the long run. I suppose a secondary theme is "salvation", although the story hasn't progressed far enough yet for the characters to see that yet. I also try to make the NPCs as complex as possible. They may be evil, or good falling into evil, but there is a reason for their fall that goes beyond taking over the world for the heck of it.