What part of the Mass Effect lore would you want to see more of? The past or the future?
"Parsing through your thoughts on the next #ME game. Would you be more interested in a game that takes place before the trilogy, or after?" asked Mass Effect Executive Producer Casey Hudson in a tweet.
Following either route would make for an interesting narrative. No doubt, developing a prequel would be the easier course for BioWare, considering that it has plenty of Mass Effect history already developed through the games and all the transmedia tied into the games. The only challenge would be to craft a narrative that manages to tie into the trilogy without bringing up any conflicting material.
Considering the drama of Mass Effect 3's ending though, BioWare doesn't seem to be the type to tell the easy story.
Making the next Mass Effect game a sequel would possibly force the developer's hand in making one of the many Mass Effect 3 endings canon, though avoiding a mention of the direct ending isn't wildly unimaginable. It would definitely make for an interesting story, especially since it would show how the universe dealt with the world post-Reapers and Reaper technology. The plot of the original three was largely driven by the over-arching threat of the Reapers, and the BioWare writers will have the freedom (and challenge) of writing in some sort of new problem that the universe must deal with to drive the plot of the game.
So what will it be, prequel or sequel? It's altogether possible that BioWare has enough fiction to develop both.