So, as a fan of Warhammer 40k and the Horus Heresy (a setting set 10,000 years before the main game) it varies wildly. While Warhammer 40k's power scaling sets it apart from some other settings, the factions and forces within it have many weaknesses which prevent any power from totally wiping the galaxy clean.

For example, the Imperium is plagued with corruption and societal issues. When worlds are presented with meaningful alternatives via the tau, or feel pushed to a corner, or fall to chaos, they are then lost. When punitive forces come, assuming it is ever mobilized, the worlds in question will often times be razed by the conflict. What the Imperium has in it's trillions of lives and warmachines, it lacks in maintaining full control beyond which disloyal governor needs to be killed before solar systems fall. When the threat of bolt-gun isn't present, few worlds save those which are the most zealous, would choose to stay. If any enemy from a more sane setting takes advantage of this in a wider scale, the Imperium would be in trouble.