Let us put it this way.
Every faction in the galaxy is either mind-boggling powerful or mind-bogglingly difficult to get rid of, just in different ways, which is why it's a balance of power that allows everything to continually teeter on the brink of destruction.
The Tau could be annihilated if anything focused on them, but because they're so small and the least likely to completely annihilate anyone else, nothing really bothers them much other than getting annoyed when they start shouting about the Greater Good.
The Imperium is fucking huge, largest anything in the galaxy, it's just that they're hyper-inefficient and strained by voluntarily fighting everything including itself. And no, they aren't the last hope for humanity. The Tau Empire is. Shut up, IG fanboys. You know our form of slavery is better.
The Orks cannot be wiped away from a planet. Like ever. You have to glass it to be sure. And sure, most of the time it's no big deal, since they're constantly fighting each other. Right until the WAAAGH happens. And then you're fucked, because there are so fucking many of them, and they LOVE to fight.
Chaos is inevitable, because the Warp, and because the Chaos Gods are fucking GODS. On the other hand, they're also chaos and therefore also fight everything including themselves.
Eldar are old as all shit and have some of the strongest psykers in the galaxy, as well as some of the most skilled warriors, but they're dying out; every dead Eldar is a huge blow.
Dark Eldar hide out in the Webway like rats and torture the shit out of anything with a libido. Yes, you must have a libido for them to torture you, no, it doesn't have to make sense.
Necrons are basically self-regenerating death machines hidden in possibly every third planet, with shittons of ancient technology possible outdating even the Eldar. And they hate all life. So yeah.
Tyranids are the fucking Tyranids man. I'd compare them to the Zerg but the Zerg were based off them, not vice versa. They've probably eaten multiple other galaxies and shit. So yeah.
Did I miss anyone?