All right, I'm in the mood for some ME4 plot speculaton. 
Stuff below is my pure imagination, so don't judge too hard.
For me it's crystal clear that Bioware's going along the spin-off route. A rather wise solution to any and all "ending" problems.
Not only that, but the spin-off can also turn out to become a solution for the original's "drama" ending!
How so?! :-o
(Wild imagination mode ON)
Let's say, that the new ME starts at the time of ME2, when players learn about the Dark Matter for the first time. Bioware can invent any other mystery, because the idea is to move the player AWAY from the known ME universe. The main protagonist will be involved in a secret project of some kind, which will result in a space expedition (Yay! New "Normandy"-style spaceship!) to the far end of the Galaxy/Black Hole/godknowswhere/etc.
Further on, the game may look like this (considering it's a trilogy):
1. Space Odyssey starts, engines fire and throw the ship to...somewhere far, far away.
2. Jumping to another galaxy is a long trip, the player gets lots of time for some on-board missions, crew interactions, first romance options, etc. It may be just like the Citadel part in ME1.
3. New galaxy! Here we are: new systems, new planets, exploration mini-games,first "Mako" missions (yeah, Bioware loves heavy BDSM! So should you!). 
4. Enemy detected! It's time to shoot some new alien bastards, tons of "kill-em-all" missions. And some drama, too. And romance, of course. With anything that moves on your ship. And around it. Cause it's another galaxy and nobody cares about old rules. Besides, some new aliens may be even hotter, than asari twins. Interstellar hardcore love! 
5. INTERESTING part (probably belongs to the final part of the new trilogy): we learn the secret of the "Mystery" (the one that started our expedition). The secret is so cool, that the crew decides to stop f*cking around sexy alien asses and jump back home and save our own galaxy from..the DAMN REAPERS-S-S! Engines fire, spaceship jumps back, the player finishes some on-board missions and marries (da-a-mn!space wedding!) his romance partner. And then..
6. OMG PART! We're back home! ..But not really: due to some space anomaly, player's ship travels through time and arrives at the time frame of early ME3! Long before the "ending" nightmare. Now the player gets the chance to do things right: dance and get drunk with Shepard (the dude is alive and well!), romance him (oh, yeah!), do some co-op missions with the legendary commander and his badass team (imagine how cool such cameos could be!) and...FINALLY..get the right ending by wiping the Reapers with the newly discovered..ehm.."Mystery" thing! 
7. Final closure for Shepard. Like really f i n a l. New hero takes his place and is ready to bring happiness, love and nuclear strikes to any world he/she/it puts boots on. Get ready for another trilogy.
8.DLC : Shepard learns you've been cheating on him/her in another galaxy. And gets upset.
That's it! Need some pizza.
Retour en haut
Another galaxy, another hero, another time.
