In a sequel I'd see two major possible big bads, Leviathans and the Reapers.
Leviathans are a threat because they are a massively powerful race capable of enslaving organics/ and if husks are any indication perhaps synthetics as well. The Keepers might be susceptible to them, and they may adopt Reaper tactics for their own benefit. They also claimed Shepard's mind, gaining access to both his/her memories and more than likely took the The Cipher. The Cipher would give Leviathan's access to Prothean thought process, language, and technology. This would mean they could quickly recover and use Prothean tech the rest of the galaxy doesn't have access to. With this and their own natural abilities they could quickly build the power and numbers they need to impose their will.
Reapers are a threat. The first game sets up that Reaper tech is buried across the galaxy. Any Crucible ending would also be insufficient to take out all Reapers, as the Crucible relied upon the Relay Network which for one... only covered a small portion of the galaxy, and two... by the events of Mass Effect 3 the network was kind of broken. Both the first and second game give examples of Relays that are either lost, disabled, or destroyed. Any Reapers and their tech in areas of space not covered by the Relay network would not be vulnerable to the Crucibles attack, this would include the Batarian worlds cut off during Arrival. There is also the Citadel. It's position made it the perfect firing point for the Crucible... but the Reapers moved it to Earth. Doesn't that mean the Crucible could only effect the Sol System connected Relays?That would leave the Galaxy full of Reapers. If the Citadel was were it was supposed to be it could easily hit the majority of the network, but from Earth I'm not so certain that was still possible. There is also the potential of more Reapers existing in Dark Space as well as the other plane of existence Sovereign mentioned.
Other than that, all of the races are recovering from the war. Perhaps this would encourage other species to become uppity. We still haven't seen the true Terminus species, and there are other species throughout the galaxy that may have an advantage of not having been immediately targeted by the Reapers. This option for a sequel, with old or new races is the one I find most attractive. But all the ideas for sequels are pretty interesting to me. There may not have been many different endings, but what differences were there do have potential.