Justice League (2001-04)
52 episodes, approx 22 minutes each, split over 2 seasons.
It's often the City of Metropolis under threat, but, while not explicitly stated, the War of the Worlds style attacks in the very first arc make it clear that the danger isn't just going to be of global origin, it'll be intergalactic.
The typical focuses are there, of course, such as the folly of those with power, the corruption of the weak-willed in the face of that same power, and the way in which good intentions ill-conceived can be catastrophic to all, but like the comic from which the show took its name the stories aren't unwilling to stray into surreal situations in its exploration of such things. JL is storytelling without constraints.