Maybe the only confirmed detail we have about Mass Effect 4's story is that it won't star Commander Shepard. Beyond that, we don't have a clue how BioWare will continue the series. They've got an entire galaxy and millions of years of history to draw on for the next game.
Here are a few different ideas that BioWare could use for Mass Effect 4 and beyond. None of them are perfect but each could make a great RPG.