They could, in theory, have created a 'ten/fifty/100 years later' sequel' with new tech, new races, new characters. Perhaps facing off against a technologically and socially-advanced Yahg? A society where the Asari have become decadent and disinterested, and the Turians isolationist, leaving a resurgent Krogan and Quarians as the new face of the Council, with Humanity as the elder statesmen?

The problem with writing sequels to games like Dragon Age and Mass Effect are the multiple possible endings they offer. DAI tried to build some variations from DAO into the game setup, as well as allowing you to load history from your DAO game. But the changes involved were generally cosmetic. ME3, however, produces four or five endings. Now the Refusal ending - which almost nobody goes for - would involve an entirely new Universe, 50K years later, with entirely different races, and having them searching for Liaras' data to defeat the Reapers - same old, same old but with different characters. The other four would require at least three separate games: one for Synthesis, one for Control, and one for Destroy and its' Shepard Lives variant. Shepard Lives would not require much alteration except for slight additions to the lore about hs later life and maybe a bonus mission.

Since Destroy seems to be the most popular ending among players, I would assume that ME5 (should it ever happen) will be based on this scenario, and will include Liara, Wrex, Grunt and possibly EDI (they could have rebuilt her a body, her AI survived, because if it hadn't, the Normandy, as her synthetic body, would have been destroyed - the same applies to the Geth, who would have backed themselves up into servers on Rannoch). But a new set of Human characters, hopefully (poor Shepard has done enough, surely?)