The game will start on Earth where Shepard will be standing trial for blowing up the Batarian system in Arrival. Just as the persecutors and the judges provide irrefutable proof that Reapers don't exist, Reapers show up and start wasting the planet. Shepard fights his/her way to the Normandy and takes off to bring allies.
On friends and allies: Cerberus and the Illusive Man will try to kill Shepard this time around. Liara, Garrus, Ashley/Kaidan, and the new guy James Sanders will be permanent party members. Wrex, Mordin, Legion, Capt. Anderson, and Udina will come back as allies, too. The game will have multiple endings, depending on who of them survives until the end.
The RP system will be expanded again to, I guess, a middle ground between ME1 and ME2: it'll be basically like ME2 but with talent trees, weapons will be upgradable again, and all classes will have access to all weapon types from the start, except that only Soldiers will be able to carry all at once. The rest will have to settle for either two or three at any time.
There won't be any multiplayer, thank gods for that.