As far as weapons/armor/inventory goes:
Don't bring back the massive inventory, it makes completely no sense as far as realism goes and is tedious as all hell. That said, there should be more variations of each weapon type for you to pick up, at least 5-8 for each type. At the same time, the better weapons should be balanced against each other so there shouldn't be a clear-cut best choice for each weapon type.
There needs to be more types of armor that you can customize. Right now, you can only add stuff to the default N7 armor, I don't know why the other DLC armors didn't come with the ability to be personalized - it seems like a really bizarre design gap.
Characters:
My personal ideal would be to have a system where you have 5 slots on your 'team' but, say, 9-10 characters you can ask to join it. They should add a few new characters for fun, or at least make one of the recurring NPCs into a recruitable sidekick (and, no, I'm NOT thinking of Conrad Verner here). And, yes, please add a Batarian, if only for political correctness. We've rehabilitated the Geth, can't we do the same for the poor terrorists? These are guys who won't think twice about turning your world into a glass parking lot, you DON'T want them on your side against the Reapers?
Story:
Ugh, I don't even want to second guess Bioware on this one. Too many possibilities. But you know what would be awesome? Making Kaidan/Ashley a second human Spectre with some rivalry going on and then a reconciliation halfway through. Yes, really. Clearly, there are a lot of mysteries that need resolution: who is the Shadow Broker, who is Miranda's dad, what's up with the dying suns etc etc.
Mako/Scanning/Resources:
My choice would be to have a system somewhat like GTA San Andreas' territory based resource thing (except without all the constant attacks on your areas) where you have to kick a Merc group of a certain solar system in order to pave the way for Alliance miners to resume work or something, in exchange for a lump sum of minerals. To change things up, make it a side quest that spans several systems - say, you free up a mine but then are asked to get a processing plant in another system online.
Sidequests:
This is the big one for me. More sidequests, longer and more complicated sidequests, more XP from completing sidquests, larger hubs (Citadel was too small, Tuchanka was tiny, Omega and Illium were disappointing) like in Dragon Age: Origins (think 3 or 4 ME1 Citadel/Denerim sized areas), and more NPCs related to sidequests and factions.
And my #1 wish:
A modding kit to come with the game so we can add our own systems and gear.
Jenova65 said:
A way higher level cap (since BioWare feel they absolutely must level cap *tuts*)
I have never understood this about Bioware, why why why. Every single game they've made I've been upset about the level cap - is it really necessary? I know the idea is that it forces you to choose between different leveling options, but it also takes out the fun of multiple replays and spending more time with the same character.