This more than likely will be handled like the new Transformers Age of Extinction movie being 4 Years after the events of DOTM, it has a brand new set of characters with Mark Walhberg replacing Shia which is a welcomed change.
AOE looks worlds above DOTM, both storywise, botwise, & character wise from Galvatron, Unicron possible being hinted on probably handled Post-End Credits such as Thantos in The Avengers did.
ME Un-Titled could be done similar being about 20 to 50 years after the Reaper Wars, with a New Cast of Characters being set in the same timeline 7 universe as Shepard Trilogy.
Like I said handled the same as AOE, Same universe, same timeline, NEW CAST, new story, New Locations.
But a game like Mortal Kombat X, is largely a unknown, many say it will be a connector to the upcoming Reboot of the Film, while others say MK X will be a Continuation fo the 2011 game, then others say the game will be something new entirely.
Cant wait, I am just glad we are both getting ME & also Dragon Age, I can play Dragon Age then next year I bet ME comes sometime in Spring 2015.
Kudos to Bioware for taking time on both ME & Dragon Age with Inquisition looking worlds above DA 2 being like WTF was DA 2 not saying 2 was a bad game, but Inquisition is going to blow that game out of the water.
Cant wait for E3, ME, ME HD, Inquisition, more Bioware AWESOMENESS, keep in mind Bioware also has a brand new IP in the works that will be neither Dragon Age or Mass Effect related.
Could this game be revealed @ E3