Prequel - No
Sequel - Yes.
The game should only move forward going back keeps all games who do so stuck in the drain of it. The game should get set 3 - 50K into the future. I would prefer a 50K route as its kind of a universe staple at this point it also gives us the longest time line that gets rid of the old cast so BW can't mess them up anymore, it allows whatever ending you picked to have a long enough timeframe so the universe will have normal looking people (if you picked synthesis) or ignorant people if you picked any of the other endings the reapers could be just plain gone long before the 50K mark via self destruction for para players or they got annihilated in another galaxy by some superior force or they got killed off regardless of past player alignment by our new badguys on the block.
I think ME4 should let us pick our species, pick our sex, have a script, dialogue, and situations set up that will also include the fem hero version fully so it works plausibly for both sexes in the moments no more butch femhero situations or dialogue moments, and we should keep the large scale save the galaxy and work more on the interpersonal relationships of hero + crew.
Dialogue wheel should come back like in ME same with large inventories but combine multiple items into one line like if I have five shot guns it shouldn't list them off one after another it should simply read : shotgun x5 they did this inventory consolidating way back in the 90's I don't buy for one moment they can't do it in current systems.
More conversational branches and convo endings like Dues Ex HR you can have multiple endings to a cono and multiple pathways some of these can be very deep like talking to the cop/ex-coworker at the police station or talking to Huge during the end of the game in his high tower. I want to use the wheel to form these relationships and its ok if they aren't always perfect
Customization options need to be expanded on I've posted a few times about EVE Online and how wow their facial and hair customization is basically for me the more realisitc and awesome I can make a hero the better it is for me and since in ME we deal with custom heads on default bodies it might be possible to do at least half as great as EVEO is for humans, huminoids, and aliens alike. I'd also like to suggest that BW have human, quarian, and turian leads to customize and pick as your hero choice.
If you bother to make backgrounds for the hero(s) then make them freaking count this time not just in dialouge but how the hero speaks and behaves if we say have mindior shep that the players set up as a hater of batarians via someone asking about mindior and batarians then our hero should be pissy at our batarian squadmate in inflection and manners unless via interaction the player picks x-amount of para options when dealing with them then the mood towards this character will change overtime, in cut scenes, and in inflection and body language.
Deeper LIs we all know the press para to win love option is totally there its a simple system but there are more then enough players who take their relationships seriously despite the simple win you can get so the LIs should be more involved after you romance them and after you make love with them simple things like changing how they speak to you on missions and ship for general things like DA had the LI calling you, " Dear" or " My love" this was cute and simple way of acknowledging you two are together and it was done every so often. The LI should show concern or down right lead rescue parties if you are introuble, kidnapped, or nearly murdered. If you disappear for long moments with no radio contact if you find them on ship afterwards they should express how terrified you made them, if trauma happens to your lead like they get hacked your LI should find you later at a quiet time in the game and want to talk to you about that and see if you want to speak them express yourself over this trauma similar to how Liara always turns up in ME3 that personal interaction and attention was great LI or no.
More variations in cutscense and personal moments of M/F heros I love how in dialogue and cutscenes we can get a 1% difference in male or female playthroughs but we need to vary them more I'm sick of people saying m and f hero can be bro and sis or distant LIs or they're the same person just in AUs. Ok maybe I'm not going to get away from the AU one but when I play as male hero I'm doing so to experience it from a males pov and I play the fem hero to play from a fem pov but that 1% difference isn't making it very huge as a fem player I can see where I should be getting grief from npcs or they should try to railroad me and they aren't maybe its society now vs the utopian society of ME where no matter your sex you're equal that is throwing me off here but I expect her campaign to be harder in alot of ways like the game Mount and Blade if you're a fem hero you work harder to be accepted as a warrior you need to do extra missions to get sponsored and taken up for training and so on because in this world you unusual. I also think in some areas your fem hero should have the advantage over male or vis versa.
Live up to your M-rating as far as situation are covered like drinking back in, ME style sex scenes in, if you're covering dark or unusual topics like mass murder or slavery then do so stop trying to make an M game that is so watered down it should be a T. M was made for adult players treat your players like adults they can handle themes or narratives that are above your PG13 shows.
More RPG less shooting and way less shooting galleries if I want to mow down hordes of mooks I've got a plethora to choose from.