A couple of hundred years had passed since Shepard destroyed the Reapers and the Citadel and the Relays had been rebuilt. The Citadel was still orbiting Earth and all of its inhabitants were tired of the same view of the Earth, so they wanted to move the Citadel to a new location. But to where? That was the question.
They had learned how to drive the Citadel and started visiting many different solar systems, but none of them was what they were looking for. Eventually they arrived to the Omega Nebula where Omega was located - but it was the worst location they had ever seen. So they'll just go through the Relay to a new location just as they had done tens of times before, nothing could go wrong, right?
Well, the male Turian and the female human who piloted the Citadel got sick (she ate the turian's sushi and the turian ate the human's sushi, both got sick) and some noob had to replace them. He only had basic training and had never flown the damned thing, but no one else could do it. The Council told him "Go through the relay!" but since he was such a noob he went through the Omega Relay (which somehow survived) - since the Normandy SR-2 was a museum located in the Presidium, the relay detected the IFF and allowed safe passage.
But the Citadel was so big that they appeared really close to the event horizon of a black hole, and funny things happen to spacetime when it is subjected to such gravity. Not even their Mass Effect fields and ezoo could save them from the gravity and time dilation caused by the black hole. For an entire month they fought against the black hole until they managed to escape from it. But remember, time was dilated! One month had passed in the Citadel - but outside the event horizon several billion years had passed.
The Galaxy was completely different - Andromeda and the Milky Way had finally collided!! There were countless new star systems and planets, while many old stars and planets had disappeared! They met met new alien species and tech, and learned of the existence of the Reapers v2, who had been created by Leviathan v2! And they were coming to harvest the entire galaxy. That is when us, Shepard v2, come into play. We must save the Milky n' Dromeda or whatever the new galaxy is called.