More specifically, how do I keep the game fun when all parties involved are extremely powerful? The game I'm asking this about is a Wild Talents 2nd Edition game where everyone is built on a budget of 1000 points. For comparison, think of a level 30 game of D&D 3.5 in terms of power level. The purpose of the game is to see how much the players can change the course of history while fighting with the supers (mostly NPC) who are at odds in the way they're changing history. The two obvious ways (Monitoring PC design and building challenging NPCs) I can do, but how do I maintain an interesting campaign over time at this level of power, without any one character finding a way to absolutely destroy any competition? This question is tagged as a Wild Talents specific question, but general answers will work fine too.
Decide to not play an indefinite campaign. Setting out to aim for an end is the best way to avoid a campaign from wandering aimlessly and ending with a wimper. With an end in sight, you'll be less worried about padding the game with "suitable" challenges and more attentive to allowing/helping the power level of the game drive toward a climax.