I am of the opinion that Mass Effect 3 was a great game, tainted by some broken promises and a hastily rewritten ending. The other 95% of the game was good. Great, even. Just that last part was kind of a screw up.
Unlike more recent disappointments (AC3), I will still plop my money down on the counter for ME4. UNLESS I detect one of the following.
#1. Prequel
As a writer, the idea of the prequel is offensive, to me. So many of them rob their prede(ante?)cessors of ontological inertia and serve as a cheap and lazy way to reset the setting so that you can have Stuff Get Wrecked from the same starting point. It is my feeling that Mass Effect does not need prequels. ME1 IS the prequel.
#2. The Tyranny of Choice
Much as I dislike many elements of JRPGs, at least they are willing to strongly characterize their protagonists (even if there's only two kinds of protagonists in JRPGs, and they're both some iteration of Angsty Male Teenager With Confidence Issues). Having another prot who's dull as dishwater boring because the story has to adapt to whether he's a humanitarian or a badass will bore me, and not get me to do a second playthrough. Skyrim is the epitome of this tyranny -- you handle your character's build and the order in which he tackles quests, but otherwise, the world would clearly turn without you and whatever choice you make. ME3 escaped that -- the choices you make matter to the Defense of All Intelligent Life fleets, even if they don't the ending. More of that, less of stuff like LA Noire.
And to everyone asking for create your own protagonist, down to species, recall that every unique beginning story/staring area, more content is going to be taken out of the middle/end of the game.