Well, I am happy that they really want to make a fresh start. That is what I was hoping for and it looks like they are going all the way.
The one thing that I am curious about and where I think there is real potential to mess things up is in how they will explain the transition from the events of the trilogy to Andromeda. This is going to be a tricky one and BW's track record in explaining transitions is not the best.
'Cause here the deal: BW wants to remove itself from all the decisions and resulting different scenarios from the trilogy (especially the ending) which is probably a good decision. At the same time, they want to keep the essence of Mass Effect intact, to which -in no small part - belong things that are lnked to the milky way, such as all the races, the technology and the organizations, such as N7, etc. The fact that they want to cherry pick what to keep is already obvious in the trailer (we see the N7 logo, a Krogan, the old suit, weapon and vehicle design and so on. It's a good thing that they are going down this route, too. If they were to completely abandon everything and start from scratch, they might as well make a new IP after all.
However, IMO, it will be very tough to find a good way to take all these good things with us to Androme while leaving the bad (or problematic) things behind while still having a believable transition between the old trilogy and the new game. And I for one would like to have some form of transition, I'd hate for them to not give us one and just say "here we are".
The problem is that BW's writers tend to go backwards in the writing process. It seems they first decide what they want and then they retroactively force-link it to previous events. Need Cerberus to have an army right now? Just come up with some reason why they are completely different from half a year earlier. Need a crucble to defeat the reapers? Just make up some new files in the prothean archives on Mars that somehow no one saw before. Need Zaeed Massani to have been the previous leader of the blue suns? Just retcon the history of the group and say the public has had wrong information. I could go on but you get the point. There isn't even anything wrong with this approach per se but IMO BW tends to be sloppy about it.
So my main concern with the new setting is that they will give us another quick and dirty explanation for why we are where we are and why everyone else is there with us, so that they can forget about it as quickly as possible. I for one do not want my first thought when starting up the new game to be "Are you serious? That's your explanation?" That would immediately sour my enjoyment of the game (just like it was the case in ME3, where I started the game and immediately thought that it was weird that I was in this room on earth with James (a guy I didn't know at all).
So making a fresh start is all well and good and I am looking forward to that but I am concerned that they will begin the game on another BS note and that would really suck. Please BW writers, take great care and time to establish this new scenario properly and with respect to what you have done before. If you can do that, ME:A can be a realt step forward in the ME franchise.