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.
That's not my point, this is my point:
That's not what he's saying, he's saying he's sick of that recycled plot that Relic has used for most of their Warhammer games ever.
Orks and Chaos are not the only antagonists in the 40k universe. Every description of the Imperium says "beset from all sides by a myriad of foes", you have Chaos, Nids, Eldar, Dark Eldar, Orks, Tau, Necron (that's 7 different factions) PLUS traitors, heretics, mutants and etc within the Imperium and the own forces of the Imperium which are at each other's throats and you're telling me that again they have to rehash the old invasion of Orks>(insert manipulative Eldar here if you want a twist)>greater threat of Chaos?
Now, I'm not saying this will be a bad game, even if its the same old plot if done in a interesting way it'll be good which I'm hoping it will be.
we could have an awesome tactical Imperial Guard FPS in the vein of Republic Commando
This.

You could easily have a Karskin/Storm trooper squad in such a game or maybe Inquisitorial Storm troopers, it would be cool a tactical game while you fight to protect your squad or yourself from heretical taints.
Damn shame Republic Commando was so short, awesome game.
He wrote the Ultramarines movei..and it sucked.
rememeber the wooden bridge thing?
god i cringed -.-
Thankfully a few scenes after that real marines of the Imperial Fists showed up and movie got better, well, at least until they died...