When you think about it, there are really only 3 choices Bioware would need to address in a post-ME3 Milky Way (assuming no Shep and co):
- RGB
- Quarians vs Geth
- Genophage
These are all big choices in the context of the trilogy and establishing a starting point for ME4, but in terms of what subsequently happens in ME4? Not so much.
I honestly feel that if they just picked canon decisions for these and then established those decisions early in the new game, this would actually be the least contrived way to have a fresh start. Once the consequences were established, the player would be free to play a brand new story set, say, 100-200 years later in the MEU. No hiding from known parts of the galaxy, no ark theory, no handwaving the endings into the same outcome.
A possible fourth choice to address is the Rachni, although that could really be ignored because ME3 already established that some Rachni survived regardless of Shep's choice in ME1. And it's not like they need to play any role in ME4.