I'd love to see a sequel set hundreds of years after the events of ME3 with something other than reapers as the main antagonists, maybe something is discovered after traveling to a new galaxy. Plus making the setting in a new galaxy would make it so that they wouldn't have to make 3 different storylines based on your ME3 ending choice.
"Immigrants. Thats all they do, you know. Just driving around, listening to raps, shooting all the jobs." - Malory Archer GT: Bessy67