Everybody has a different opinion on what to do, so no matter what Bioware does, they will make some people unhappy.
Bioware could very easily hide all the endings in the plot of ME4 and make it ambiguous enough. The reapers did a real number on the galaxy, regardless of which ending, so much of the history is lost to time. Some may say that this is running away from the problem, or not satisfactory, but those reasons wont keep it from happening. They can just set it a few hundred years later.
There will certainly be a legend of the Shepard, but it will be vague. Everybody knows that Shepard saved the galaxy once, and that's all there is to it.
I vote they try to make an ambiguous story involving all 3 endings in a game taking place a century after ME3. It would be a massive undertaking to try an develop a whole new series that can use all 3 endings of the old series.
First of all, not all the relays activated as planned. So there are areas not effected by colored light. That leaves the door open for some things. That also allows for some galaxy travel. The relays do get repaired in 100 years, thanks to people finding how they worked. It is not disclosed whether or not reapers helped. You will find a large group of synthetic hybrid races, and that all of them seem to be from a similar religious sect. But whether these beings were created by the crazy light or went about doing this on their own due to their religion is not covered.
It is possible we might see other galaxies in Mass Effect, thanks to a super secret relay the reapers built that hops over to other galaxies. Thus these galaxies would be in the game along side ours, this is not the arc theory thing. Doing this allows for a lot of things. Much of the game takes place in the new galaxies, so the events of the Milky Way can be left behind. You are too focused on exploring, meeting new aliens, and other fun stuff to talk about things that happened 100 years ago. It may very well be the player character in this story who finds these relays.
By going to the new galaxy, you can have all kinds of cool ideas. There could be an invader angle to work on, as some species try to colonize it. Then you unknowingly uncover a new big bad guy, who threatens everything...again. And we have to remember, if there are relays to other galaxies, then there are certainly reapers in those galaxies as well. For the sake of plot, these reapers may not have been effected by events in the Milky Way (so the destruction ending is covered,) and have even evolved differently. But in a plot twist they wont be the bad guys. The magic of this plot twist is that it could just be Shepard's Reapers, but we will not know for sure.
That is how they can cover all 3 endings. I am not say this is what they'll do.
When it comes to the various species that Shepard could wipe out, they will mostly be MIA with little explanation. However, that does not mean will not see a character based off them. They can use any plot device as an excuse, like some character was in stasis and not effected by any possible extinction. The Krogan are plentiful enough in the series even with the genophage, they wont be going anywhere, but nobody will speak of it, either.