Having a tragedy take place under the reveal of the new villain would be following in the footsteps of the original trilogy, but it would be something I would consider doing. There are too many loose ends to kill Ryder off, but having to face the consequences of using the kill code, killing the cardinal, or a mixture of things that results in the deaths of multiple characters, both companion and side would be interesting. It would certainly make any actions you then take justifiable; you could always then do a revenge story where Ryder gets stripped of the Pathfinder “rank” (But still is connected to SAM) and continue without the backing of the Initiative, then a new character be the next Pathfinder similar to how Dagon Age handles PC’s.