Sure Prequels have problems, exspecially if the focus is on characters you already know about who exist in the original work, so you know they cant die. However if done well, a prequel can be good. Personally I prefer prequels who focus on completley new characters (therefore not knowing their fate) and done in a way in which this new story can be great/exciting, without feeling pathetic since you know the future.
I think what would benefit a mass effect prequel, if is the main character isn't human. Take a different path then the original ME trilogy and ME Andromeda. Allowing the main character to be an alien, opens up much more space to be explored (Rachni Wars, Krogran Rebellion, etc). I think there is potential to even see the previous prothean cycle, whether that be in a future game, book, comics, animation. If we ever see more of the Prothean cycle, I dont want to see the Protheans get wiped by the Reapers, but see more of their world, the many other species, the non-Reaper enemies they faced, etc.