New Vegas was also recently populated by three tribes that swore allegiance to House. And House also still has the Securitrons. Not to mention the NCR are nearby and even have an outpost there. Between the two, they have more than enough manpower to sweep the slums clean; the only reason why they haven't cleaned up the place is due to sheer apathy, since cleaning up Freeside and fortifying it for defense against the Legion is a sound strategic move.
And? Bethesda were tasked with making a Fallout game, and they delivered. It's like when Intelligent Systems were tasked with making a Mario RPG, and the final boss for the first game in their Paper Mario RPG series was Bowser, AKA the final boss of most Mario games. After the success of their first Fallout game, they started making their own factions, like the Institute, the Railroad, and the Minutemen, with only the BoS as the legacy faction since even Interplay had them around for at least four Fallout games before selling the series to Bethesda.
Not to mention the fact that two out of four Interplay Fallouts had the Super Mutants as the bad guys. So again, it's not like Interplay didn't do the same with Super Mutants when the Master was already beaten in the first Fallout game.
Again, the most Obsidian were able to make when tasked with making their own continuation to Fallout were A) Rapture on the ground with a capitalist version of Thrawn as a battle droid commander, and B) every evil empire trope rolled into one tribe. And given what they did with The Outer Worlds, giving Fallout to them and letting them come up with a new villain would have probably ended with a stereotypical corporate asshole faction that we've seen in countless RPGs up to date. The kind of assholes that Commander Shepard from Mass Effect or Revan from KOTOR would either work with or genocide on their way to real problems.
But I'd like to hear from you guys. What would YOU make as a new faction if you were given carte-blanche by Microsoft and Bethesda to design a Fallout game, with no limits attached?