Being Required to Play Multiplayer - This will immediately deal-break. Personally, I think they should forget multiplayer entirely, but I doubt that will happen. In this case, don't force me to play it, don't require me to play it to get a better ending. I should be able to ignore it completely if that is my desire. If I wanted to be forced to play multiplayer, I'd buy an MMO. And I've never bought one.
Right now, that's the only one they could do this early. Once the characters and trailers are released, there's a few things that'll make me say "no"
Making the story all about krogan - I'm really sick of hearing about the krogan. The cliched warrior race space orcs were nothing more than annoying, and I always felt like the game was shoehorning me into thinking "The genophage is bad!" I don't want a krogan storyline. I don't even want a krogan arc. I especially don't want any other race subordinated into being nothing but a satellite for the krogan, as the salarians (the damn Council race) were.
Creating another Mary Sue - Liara was easily the worst character in Mass Effect, and possibly one of the worst BioWARE characters of all time. And all I kept hearing (from me, the character I'm controlling) is how much of my friend she is, how lovely she is, how the asari are so great...If I don't like a character, don't make me feel otherwise. Don't make me think a character is my bestie, especially if it's not important to the plot if she is my bestie or not.
Make the characters relevant - This only applies to required characters. An optional character doesn't need to be relevant, and if they aren't, that's fine. But if the character is supposed to be part of the story, give a reason for them actually being there. ME1 had literally zero reason to need Liara, but I was forced to take her with me. That was true again after Mars in 3.
Deciding that Diversity = Great Characters - I was very bored with the character of Krem and thought the character was utterly forgettable. But then I started seeing the tweets and other releases from Gaider and Weekes, and I was concerned. They seemed to think it was inspiring and the greatest thing ever that they did it. I saw it again with Dorian (another terrible BioWARE character) when Gaider said "Oh, he's gay, but he can kick ass" was the extent of his character. I'll say it plain in case they read this: It's not. If that's the only thing you can say about any of your characters is they're this orientation or that, and the representation is needed, then you've failed as writers. This isn't some parade where you need things like that: Your job is to make rich, deep characters. Unless you're writing the ship's prostitute (and even then), there is a character outside of orientation. If the orientation is a distraction, don't do it.
Too much "Humanity" - I can accept Kaidan's philosophy that aliens are nuanced like humans. But they also grow up in a culture that's completely different. I don't want to see asari as blue humans, turians as bird humans, and salarians as frog humans. Give me creatures and philosophies that are alien.