If in 40K, the Reapers would eventually get raped by the endless numbers of the Orks. To give you an idea, several probes were sent by the Adeptus Mechanicus to scan for signal coming from the other galaxies of our supercluster.
They found signals. Lots of signals. An enormous amount of signals from each galaxy.
All of them are Ork signals.
Yeah.
...
I'd theorize, instead of restarting the calendar at 1 AD, because it's the 41st millennium of the Christian calendar (not that anyone remembers it), the following.
Keep human history as normal for 40K. Add the Citadel and associated species, Terminus Systems and all. We know little enough of the Age of Technology to insert that without trouble.
Here's how it changes. The Reapers are the automated armies of the Eldar Empire. It allows both the indoctrination tech and the creation process of the Reapers to find origin in Warp technology and explain their quasi-supernatural ability to subvert minds. By the same token, the central intelligence Reaper are created from the sheer agony and hatred of an entire species being slaughtered as seen in the Collector base.
The Reapers therefore become the instrument of the Eldar to cleanse the Galaxy of new species, both ensuring their dominion and diminishing their influence on the Warp. Mass Effect tech provides a nice, low powered tech for the new species to concentrate on, diverting them from Warp tech. The added bonus being that the new species, being regularly exterminated, have less chances of waking the slumbering Necrons and, for plot-related reasons, explaining the lack of major species other then Mankind in the Milky Way in 40K.
Mass Effect happens as normal, Shepard being either an extraordinary man or one of the many personae taken by the Emperor through the ages. And so, the Mass Effect trilogy represents the first hiccup in the time-proven cycle of the Reapers, what follows is the constant conflict of the Humanity-led Citadel against the Reapers throughout the Age of Technology.
The war continues during all of the Age of Technology, species dying left and right to the Reapers with Humanity holding on first by the skin of their teeth, then with increasing confidence as they diversify from Mass Effect tech, eventually discovering Warp tech and other more esoteric technology from 40K. Of course, by the time they do, most Citadel races have died off in one way or another, leaving Humanity the last man standing with the Geth somewhere around M20.
In a last ditch attempt to kill Humanity and the few remaining races, the Reapers manage to subvert the Geth with their dying breath, thereby explaining the Iron Men rebellions of 40K lore.
As the war with the Geth finishes, Humanity tries to unify its territories... But the consequences of destroying the Reapers finally manifest as the careful equilibrium that allowed the Eldar to slide slowly into decadence without troubling the Warp too much is broken by the added emotional influence of Humanity. The Eldar Empire falls into complete decadence by the feedback from an increasingly troubled Warp and Humanity fractures irremediably as the Age of Strife begins.
