My opinion:
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What I hope it won't have:
The N7 guy as the main antagonist. Please don't!
If there's one thing I really don't like on game franchises when you change protagonists is to circle back to what you already did or been, in any form.
Been a N7 for three games and in the fourth we need to defeat one to earn our own N7 status at the conclusion of the game. It will suck.
Mass Effect doesn't need to have N7 as a central theme, as a symbol of achieving the hero status. We could already be one from the start, of course, but please, not "the N7" main thing.
The hero journey doesn't have to be that cliche. We need to develop ourselves as a character differently from Shepard.
Been there, done that!
Similar thing happened in Dragon Age.
You defeat Corypheus in a DLC and he returns as the main antagonist in the next game for you to defeat again. Maybe fully powered, with elven and blight magic further enhancing his abilities, but it's not the same as fighting a new, more powerful enemy (like the Dread Wolf perhaps). It would've been better if he was a sidekick, working for something greater, far worse from the Fade.
And I don't want to go to Andromeda because we were escaping the Reapers, regardless of how your own motivations for entry in the ark, creating it to flee the impending doom just sounds like a cowardly start.
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What I hope it will have:
The reason for the trip to be one of expansion, discovery, curiosity, etc.
Unknown enemies, unknown species. The objective to establish a home for humanity at its core. Deep exploration, adventure.
That feeling of discovery, of finding things no one found before. Being not just a soldier, but also a traveler, a scientist, a scholar, a strategist.
Shepard just seemed to solve all his/her problems with brute combat ability. I want a protagonist that is not only combat talented, but also has a brain.
A decent ending! To me, the destination matters the most, and the journey must be with your own choices to achieve that.
Maybe you just want to be evil, heartless, so you should be able to. Maybe you want to be friendly with everyone, caring, worried about the feelings of others, so you should be able to as well. That means more FREEDOM and CHOICE for your character.
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Most of my other worries have already been covered in this topic.