Destroy's biggest issue isn't the destruction of the Geth, but the destruction of the Mass Relays. Basically every one in a cluster is now isolated. FTL travel is an option but it would take several years to travel from one cluster to another.
That's not an issue, it's an opportunity. Mass Relays were a crutch that limited species as much as it advanced them. To lose or have them be heavily damaged means breaking that cycle of dependency and forcing them to create a new means of FTL.
ME was in large part about discovery. We the player were new to this Galaxy as we're humans at large within the setting. It was a journey of discovery, learning what was out there and what other shorebird were like as well as what it meant to be human in this much bigger universe. By ME3's end that's not so much the case. We've traveled to every corner, learned all about the current societies and governments of the Citadel species and beyond. It's not a new or foreign setting for us to explore and discover.
To me an ME4 is an opportunity to recapture that sense of discovery and newness. It's an opportunity to explore the aftermath of an unimaginably huge war that destroyed and irreparably damaged core pillars of galactic society. How would different species, societies, governments and the like react and deal with survival and how would they change and adapt to the challenges that faced them when the foundation of that galactic society is no longer what it was, fracturing and isolating then from one another.
Losing all or much of the Mass Relays would be one of the best ways to kind of reshuffle the galactic order. An opportunity to merge both the familiar with the foreign. If handled right and given proper care and attention to exploring how different groups would handle this, we could get a setting that is both recognizable yet fundamentally changed and different.
New governments and cultures could develop within previously known ones. The fracturing of the Galaxy could result in multiple diverging paths of the same species. How would one region and community of Turians or Salarians or Humans cut off from the rest of the Galaxy for an extended period of time respond to the challenges they compared to another group isolated somewhere else?
And how would all of these groups react when finally reconciled and reconnected with the larger galactic community. How would a century or more alone and cut off shape their new culture and society. How did their struggles to survive, the not knowing of what really happened to the Reapers, if anyone else survived and so on.
Plus there's then the other 99% of the Galaxy that was never explored as the Mass Relays provided no access to them that could be opened up by developing a new FTL system. New Allen species, new cultures, governments and technology developed independent of Reaper tech.
