The trouble is that there's no way to really progress a story with a single antagonist.
If you only use the orks, yay greenskins all the way thru. Same for dem chaos boyz and dem Eldar. It's boring.
The problem is that no one other than the IG works on the scale that the Astartes do.
The Eldar like to sneak around and manipulate, that's they're schick in a story more. They're devious and manipulative, more out of arrogance than any actual malice. Also, while they probably could make mince meat out of the Space Marines if enraged to the point of direct war, they haven't marched on a planet with conquest in mind for thousands of years.
The Orks are large, and do things BIG, but you don't fly around to a half dozen different worlds during a campaign and fight a green tide that all pay homage to the same Warboss. The Orks don't work that way, and because of it, they're not a "large" threat. Certainly not capable of being the big bad for a whole campaign.
Chaos does thing big, but like the Eldar they like to skulk and corrupt before revealing themselves. And when they do reveal, they have a tendency to do themselves in with infighting and backstabbing. Again, not a good basis for a singular campaign villain.
To tell an engaging if not actually interesting tale in a campaign, it takes more than just one of the enemy races. Because none of them are a whole villain.