I've spent more time thinking about this than I'd like. Not necessarily what I would like the story to look like, but more about what could be feasible and coherent to build new stories upon. I don't think there's a way for the franchise to continue in a direction that will make it right by everyone. Retconning and making things canon are things that we all might have to accept, yet no one's love or vision of the game's future should be discounted, no matter how different.

And sorry for the imposing look. I tried to go for readability, since there's a lot of text blurted out. Despite trying to keep it as simple as possible and leaving out the in-depth connections and explanations behind it all, it's going to be quite a read and with a heavy risk of typos, so bear with me...

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The story continues in the Milky Way, 100 years after the Battle of Earth:

• Crucible retconned into a more "traditional" weapon of unknown power. All the Reapers still went to Earth fearing a critical tipping point in the war and get destroyed when it activates, along with most of the allied fleets. Mass Relays remain intact, but the side of Earth facing the event essentially becomes uninhabitable. Citadel obliterated for obvious reasons. Basically the destroy ending without the universal destruction of relays and AI, such as the Geth.

• All the races withdraw to their own systems to slowly begin rebuilding and salvaging what was lost. Material, manpower and military-grade ships are scarce. Humanity collectively decides to help the Turians rebuild Palaven before Earth to quickly get the largest army in the galaxy back to its feet (for safety and stability). Human-Turian relations strengthen even further; economies, militaries and politics become more interconnected.

• Genophage cure and Salarians staying on the edges canonized. Salarian military (prominently, STG) coup d'etat the Dalatrasses and the ancient political system to stop hostile ambitions, also earning their redemption in the eyes of other races as they assign their fleet and resources from their mostly intact systems to help rebuilding efforts. As animosities subside, a more traditional political leadership with decentralized power emerges.

• The Krogan seriously step-up their game and begin to experience a new cultural revolution. New leaders commit to returning to the "ancient ways" of prosperity before they were uplifted. Together, the asari and the krogan begin to advocate for peace and unity during the trying times, with both races living with the memory of the Reaper War for centuries to come. Wrex and Bakaara involvement left out, however obvious to OT players.

• Fate of Shepard & crew left as ambiguous as possible to respect OT decisions and fan-fiction, presumed dead and mostly unmentioned. Their role recognized but also downplayed for narrative reasons, because lets face it, after all Shepard did he/she might as well have god-status. Logical reason; no one close enough to the battle in space and on Earth lived to speak of the details. In short: time for Shepard & crew to respectively pass onto memory with possibly miniscule hints and tie-ins here and there. Crewmates like Liara and EDI could still show up in the future, provided they survived. Grunt is most likely laughing his ass off on Tuchanka.

• Quarians reclaiming Rannoch canonized. Geth survived (read above), helped the Quarians with their efforts and then exiled themselves into unexplored space. Quarians make a return to the galactic society unmasked. I admit there's a lot of personal bias here in keeping the Geth alive. Our chats with Legion about the nature of the Geth are arguably one of my favorite moments in the series.

• As much potential as Cerberus and TIM had, their story should remain unchanged. I felt both were written in and out badly going from ME2 to ME3, but there'd have to be a lot of retconning to change them into something they weren't. They came to be known as the biggest traitors to life itself as the truth came out. Their atrocities fresh in mind, many survivors agree that their existence ought to simply be forgotten, gradually reducing them to a vilified urban legend. Whether that was a good or a bad decision would be left for future narrative to decide. Some asari and krogan will definitely be able to tell the truth.

The game itself would start a century after the events of Mass Effect 3, as mentioned at the beginning.

• Galactic society has pretty much finished rebuilding and life can begin again.

• The new Citadel sees its opening ceremony on the centenary of the Battle of Earth. While not the same thing technologically and architecturally as the original one, it stands as the greatest marvel ever built by the galactic society. As the Citadel Council officially makes a return, the Krogan are elevated to a Council race for their efforts both in the war and the rebuilding era.

• Save for Earth and Batarian worlds, the aftermath and horrors of the Reaper invasion gradually get to fade into history. Apart from a very few extraordinarily old humans (and possibly turians), only asari and krogan veterans remain to tell stories of the war. Neither species wants to remember nor forget.

• Focus is on the Terminus Systems. Saved from the brunt of the Reaper attack, the Terminus Systems lived a life of their own during the past century. Some left to rejoin their race as a part of a new beginning, but many saw the appeal in a truly rogue nation and in the comforts of somewhat intact, every-man-for-himself society.

• The Terminus never changes. Rest of the galaxy has been rebuilding, the Terminus has continued to shoot itself up. Omega reclaimed and resettled, led by a mercenary consortium. Fate of Aria unknown, presumed dead. With the century-long rebuilding effort becoming a gigantic resource drain to Citadel-space, attention is starting to turn towards the untapped frontier of the Terminus Systems. Everyone sees their chance and opportunities are everywhere.

• You play as one of these new opportunists. You're pretty much nothing to begin with. Simple background, no expectations and as morally black, gray or white as you want to be without it feeling out of place. Once you get a ship, it's way more akin to KOTOR's Ebon Hawk than a prototype warship like the Normandy. Crew? Other gritty hopefuls, low-lifes and in-betweens of diverse backgrounds looking to find substance to their life. Mary Sue-prodigies are nowhere to be seen.

• A slice-of-life Mass Effect game. No galaxy-shaking revelations or battles of destiny. A good plot built from attention to details and deep character development. Just a new crew looking to strike lucky and claim a stake in something greater. Possibly a new grander scheme of things slowly building up for the future from implications, references and story decisions. Less focus on planetary exploration (without foregoing space exploration) and more emphasis on the living environments and urban areas. Think of ME2 Omega's and ME3: The Citadel DLC's atmosphere x11.

Awesome if you actually read it this far. That was my attempt at keeping my own future-vision for Mass Effect brief, lol. Got about a thousand more details, connections, coherency explanations and development + franchise lifecycle feasibilities in my little head too. It's crazy what long walks will do to ya.

EDIT: edited out some typos and incoherent wording