Warning, these ideas may have spoilers for the Mistborn and Mass Effect serieses!
Idea 1: Mass Effect 3 without Shepard
What if the suicide mission of Mass Effect 2 was just that, and Shepard, along with the rest of the Normandy's crew, died in the process of destroying the collector base?
Earth would've been taken, and the other races of the galaxy would be unable to put aside their differences and prejudices to hold together against the reaper threat, while Cerberus would grow in power, constructing their own Crucible and taking the Citadel.
The fate of the galaxy would depend on a varied group of citadel residents, from a veteran Turian C-Sec officer, past his prime, who avoided the Cerberus attack due to an injury, to a Batarian refugee who hoped to leave his slaver life behind him, to a human who's been seeing a mysterious child around the citadel who seems to have some ability to control it and helps him from afar. They would have to survive Cerberus purges, gather equipment, and, when the crucible and citadel meet above Earth, fight their way to the core to stop the Illusive Man and Kai Leng.
Idea 2: Mistborn
Essentially, what if the Lord Ruler allowed technology to progress in order to help preserve mankind, and it had reached the level it is in the Alloy of Law before the resistance attempts to overthrow him?
Both existing characters, possibly with some changes, and new ones, would be allowed, and they would be trying to overthrow the Lord Ruler amongst the skyscrapers and slums of the vast city, using both allomancy and gunpowder.