I can only really see them going in three directions with this
I could see a 4th direction, let's call it the Orson Scott Card approach: Tell a new story within the same timeframe of one you've already told.
For example, following new characters in a new story while Shepard & company are tracking down Saren (so, ME1 time frame). Or to use an in-game example, we know that James Vega had a tough mission of his own during the events of ME2. And of course, there's that 2-year gap after ME1 (though the comics have filled that in a bit).
I actually like this idea, as it suggests there may have been many such stories occurring parallel to Shepard's that are just as important and striking. You could throw in some character cameos from the main trilogy to seal the deal
On preview, this might also fit well with Demiurge's suggestion.