Alright Bioware, or, Bioware Montreal. Here is what I want to see:
(1): Let us choose the race and gender of our character. Particularly Turians, Quarians, and Krogan. Those are the three main races I'd be interested in seeing. Don't just make us play some boring-ass human. Humans suck, and aliens are where it's at. Let us play as one of them. Keep the humans as an option, not as the only one we have.
Better yet, take a leaf out of Dragon Age: Origin's book, let us have a backstory for each race too. If we can choose said backstory? Oh, all the better.
(2): More emphasis on good characters. The characters are one of your strongest points so far, though even then, it's hit or miss. For beloved characters like Garrus, Tali, and even Liara, you have your Jacobs and Kellys. You should definitely bolster your storytelling, but good characters can help big time. Of course, well-written romance can help too.
(3): Give us more choice. In fact, this ties into what I essentially want to see: Your guys version of Skyrim in space. Give us your universe, some sort of peril, be it big or small, galactic or personal, and let us pretty much plop our fan-characters into it. Hell, let it be a galactic sandbox, where we can play as Mass Effect aliens in more than just your version of Firefight or Horde.
(4): Add more RPG, but keep the shooter mechanics from Mass Effect 3. Now, the RPG aspects of 3 were there, but also kind of sparse. However, the way the guns handled, the abilities worked, and overall how the combat played out, was fun, and it worked. The only thing that would be better is less absolute need for cover.
If you can keep the combat mechanics, and add in more RPG bits to even it out, as well as complement what combat there is, you will be golden.
Now, really, that's just what I would really, really would like to see. And I also highly doubt that's what would happen. But, a guy can hope. As someone who loved Mass Effect from the first to the last game, so far, I want to explore that universe more. Doesn't even have to be with Shepard.