I'm... more than a little apprehensive. If they set the game after (even way after) ME3, then they would either have to declare an ending cannon (which would render the already pointless ending choices moot) or basically build 3 games. If they set it before, there couldn't be humans. Unless they set it less than 40 years before, in which case they would be falling into prequel territory (please god no). I've seem some articles speculating that it could be fun to have a game set during the first contact war (terrible idea, it lasted 3 battles and has already been well explained/explored) or one of the other wars mentioned from before, which would, again, preclude the inclusion of humans. All of those would be bad because they're forgone conclusions. Yeah, "it's the journey, not the destination" and all that, but it's just an unnecessary limitation. Also, we know the main character will be voiced (which I'm a fan of), and that means either we'll have a human who sounds the same as a turian and krogan (especially jarring if female), or they'll have a ton of voice actors for the main character. I just see so many logistical issues...
Finally, if they opt to avoid all these issues (other than the VO) by setting it *way* outside of the timeline of the story, it's basically just a new game recycling the existing lore and coasting on brand recognition, in which case it might as well just be called spin off. I'd rather they just made a new series, to be honest. This trilogy (baring... that one part...) works perfectly fine on its own, and there's not much reason to keep milking it (from a consumer point of view, EA will obviously milk anything it damn well pleases). I really hope they prove me wrong, but... well it seems like quite a challenge.
Finally, if they opt to avoid all these issues (other than the VO) by setting it *way* outside of the timeline of the story, it's basically just a new game recycling the existing lore and coasting on brand recognition, in which case it might as well just be called spin off. I'd rather they just made a new series, to be honest. This trilogy (baring... that one part...) works perfectly fine on its own, and there's not much reason to keep milking it (from a consumer point of view, EA will obviously milk anything it damn well pleases). I really hope they prove me wrong, but... well it seems like quite a challenge.