I mean that a race that has extragalatic orgins came into the galxy and started to wipe entire races from the face of the galaxy the way the Covenant nearly destroyed humanity in Halo.. They would glass every world each race lived on until the Federation and perhaps the Klingons were left to fight this superior enemy. Then the Federation could find the enemy's weakness and win back the territory that was lost to this race.
The reason that works in Halo is because it was all backstory. Nobody cared about any of those planets because it all happened offscreen before the start of the first game, the numerous glassed colonies were never even detailed really until Nylund wrote
"The Fall of Reach". The reason it wouldn't work in Star Trek is because it has a 40 year history with each of these races, people care about and identify with the individual species shown in the series and movies. Not to mention that it would inevitably lead to the writers writing themselves into a corner.
What you're describing has already happened in Star Trek, three times. The Terran Empire of the Mirror universe, well on it's way to becoming an analog to the Federation under Spock's rule, was annihilated by the Alliance (Klingons, Cardassians, et al). Earth, Vulcan, Romulus, all were rendered uninhabitable, and Vulcans/Romulans were practically extinct if I remember correctly.
Otherwise, that was the entire point of the Dominion War. In fact, the Dominion, when faced with the betrayal of the Cardassians, began bombarding their cities and attempted to wipe out their species. Cardassia was left a burnt wasteland at the end of DS9.
The third example is SFB itself. A major conflict in SFB is the invasion of the Andromedans. They wipe out practically all resistance in one of the Milky Way's sattelite galaxies and use it as a staging ground to invade the Milky Way proper. They're only even slowed when practically everyone and their dog unites to repel them, minus the ISC, who were hit first and by far the hardest. It's been said that Taldren had intended the Fed campaign in OP (or SFC4 before it was a Dynaverse project) to be based on the Andromedan conflict.
Now, I'm not saying that it wouldn't be fun to kick some covvie ass in SFC. But that kind of conflict has already been chronicled. As for the origin of said invader: The Covenant were from the Milky Way,
The Flood was from outside the galaxy.