1. My largest concern is simple. Don't bite more than you can chew, or over-promise and under-deliver. For example, Casey Hudson was quoted saying that ME3 would not have an A, B or C ending, that it was the end of the series so they could leave the saga on a fairly definite note for individual gamers, and even if the ending isn't happy, it'll make sense. What we got was Red, blue or green and an ending so full of plot-holes that they had to add on a free extension to it (for which I'm grateful,) but that still does not address what was actually hyped up pre-release.
So to keep it simple, don't reach out and say something will be in the game that isn't in it, or at least address it and say that the content had to be removed due to time constraints, allocation of resources, or even as simple as the system can't handle the vision created.
That, I think, was a big part of why a lot of content that was shown off by Bioware for Inquisition never made it into the game, the siege of Crestwood being on my mind, because the game was released on older consoles, the 360, and it couldn't handle all the content that the Xbox One or a high-end PC can. And this in turn led to several beautiful areas I could explore, and not much motivation to beyond my own curiosity and an OCD to be a completionist.
So, if you show it off, I want it in the game.
2. My next biggest concern is the quality of writing itself. Because Bioware has decided to set this game in the Mass Effect universe, even if it's in another galaxy, it still has to follow the rules set by the lore and three games of Mass Effect.
So the trip to Andromeda has to be addressed. Why did the humans, and whatever races come with us decide to leave. (There's a Krogan for a very brief moment in the trailer.) How did they get there? It's established that standard FTL drives aren't enough to get regular ships from one end of the galaxy to another. Such a trip would take decades, maybe even centuries to complete, and that's why there's a huge reliance on the relays. So if our protagonist is landing in Andromeda, they'd either need to construct a massive relay, find a wormhole, or probably be the descendants of several deserters who chose to flee the Milky Way and the war with the Reapers and seek out a new place to settle, and have been pulling a Quarian act and living on the ship until they arrived, generation after generation.
The last bit would explain why it would be centuries later, that's how long the trip would take with standard FTL technology and still have the barriers, carnifax and the Mako.
Essentially, I'm concerned if they'll be able to tell a great story that somehow or other does not conflict with the established lore.