Lazarus'd- no, cloned, yes!
I'd love a ME4 where Liara clones Shepard a few hundred years later, teaches via Okeer's method based on info and personality gleaned from her mind melding trick and maybe Javik's memory shard - all because the Catalyst/Reapers were actually a corruption of what the Leviathan creatures created, brought about by a multi-galactic race of AIs hell bent on forcing the Universe to conform to their idea of what's proper..
The gist of it would have: Shadowbroker Liara discovering hints about the real truth about the Reapers; Shepard being recreated; exploration of the Milkyway; discovery of a Super Relay; Shepard deciding to either destroy the SR (then retire), or use it to go on a quest to save the universe from the evil AIs (perhaps never to be heard from again). Of course there is always the possibility of killing off Shepard instead if the player didn't recruit the right team, etc.
There would not be any need to invalidate lore but it would be necessary to either make the best ending of ME3 canonical (that's the one where Shepard destroys the Reapers and has enough galactic readiness to be shown the breath scene), or work around the Control and Synthesis endings (should be easy to do since either of the science-fantasy endings can result in the knowledge of all the previous cycles becoming available, and there has been enough time to figure it out).
The few hundred years time lapse makes it easy to dump all but the young Asari, Krogan, and synthetics; and dismiss the events of the ME Trilogy as being inconsequential in ME4. Liara, Grunt and EDI (Joker made sure she was repaired, if necessary, but she may not have come back exactly like she was before) would be the only potential carry over of significant NPCs from the ME Trilogy.
Another adventure with Shepard, in a story with a better ending than ME3, that furthers the exploration of organics vs synthetics, transhumanism, and authoritarianism... I'd probably pre-order that (for-sure pre-order, if a reasonably priced trilogy-to-complete DLC upgrade was released beforehand).