For all the things that will be the same in Mass Effect: Andromeda, there's wayyy too much that is different for me to squeeze into a title of an article. The biggest, and perhaps best change is that the class system is gone. According to Game Informer players will be free to customize their character from any of the various classes as they please.
To quote the developers in their Game Informer interview, this game can essentially be summarized as "The (much improved) Mako of ME1, the loyalty missions of ME2, the multiplayer of ME3". That makes sense as who wouldn't strive to make a game that's the best features of all their prior games?
Let's start with the story. In Mass Effect: Andromeda you will control the "Ark" for the human race. There are 4 Arks in the game and each thousands of one species for means of colonizing a new world. Your character (Scott or Sara) Ryder is the child to Alec Ryder who is the Pathfinder of the human Ark. I'm guessing that considering the new trailer says "you are the Pathfinder" means that eventually that control will be passed onto you.
One thing the developers seem to want to stress is "discovery". As this is a new galaxy, there will be many new alien races that you will be encountering for the first time. Don't expect a ton of call backs to other races on the planets you travel to, as the team wants each planet to feel truly "alien" and lack any familiarity from past games.
We've announced prior that Paragon vs. Renegade choices would not be returning, and that players will have more of an ability to express themselves. This means players will be able to act or say how they feel without being cornered into one way of thinking or another...but their statements will have an effect on the game.
Relationships are supposedly more broad than ever. If someone wants to strive to sleep with every character they can in the game, that's still an option, but there's plenty of options to have platonic friends as well.
Honestly, that just touches the surface of all the things that will be in this game, but I think they're the most important. If you're looking for a more comprehensive list, check out this NeoGaf thread which literally lists every individual change you'll find in the game.
Mass Effect Andromeda is launching early 2017.