Definitely my Mass Effect campaign for Cortex Prime.
The idea was that we'd play it when the one player who has a bizarre and ineffable dislike of Mass Effect (I think it's mostly because he can't play a Krogan and feels like Wrex is, as the kids today say "mogging him", sigh) wasn't around, which at that time had been "quite often". Except that due to the pandemic he had a lot of time on his hands, so after one session (which everyone present loved) we ended up playing a lot of D&D and the campaign was on hold, and then after that we started playing Mothership alongside other games, which kind of occupies the same space Mass Effect would, and I didn't want to tread on that DM's toes by suggesting we go back to ME some of the time or something.
I spent weeks setting up the campaign, too, and had an awful lot of I think good ideas for what we could do and where we could go. I also spent a fair bit working out Cortex Prime rules for Mass Effect, which were pretty good and certainly functional for what we were doing, but unfinished. The PCs were a Salarian tech-genius, a Krogan biotic and Drell infiltrator (who remarkably, wasn't based on Thane, and that player had never even played ME2).
The basic setup, if anyone wants to steal it was (requires some in-depth ME lore knowledge I think though):
1) Start towards the end of ME3, after the Arks had left for Andromeda, the PCs are a team reporting to a Turian Spectre. The PCs are sent to investigate reports that there was another Ark, which hasn't left, and the Spectre wants to know if this Ark really exists, why it didn't leave even though the rest did, and about the Ark's capabilities (in case it can be used in the fight, or to help maybe some people survive, etc.)
2) The PCs track down the Ark, in a series of adventures, which had been stolen and was basically being filled with wealth and treasures by a loose and fraying "alliance" of mega-rich wankers who were going to use it to take themselves and their wealth (and mercenaries and weapons) to Andromeda.
(Part of what I was going to do here with these early adventures was reinforce how long-distance travel worked in ME, because that will be important context for later.)
3) The PCs (hopefully) defeat the wankers (this was more scenario-y, because there were a lot of moving parts, and ideally the PCs would be able to pit the rich guys against each other) and manage to claim control of the Ark, just as all hell breaks loose because the actual ending of Mass Effect 3 happens (Red/Renegade, of course, I mean, like 70% of players picked it first time and it's the most game-able one), which is to say basically all the long-range interstellar transport architecture of the galaxy is destroyed (the Mass Relays) in the process of destroying the Reapers and just of stuff explodes in general. This means almost no-one can travel further than a local cluster of stars (because of the way Mass Effect drives work), so the galaxy is going to kind of fall apart.
4) The Ark the PCs have, though, has special engines which can travel indefinitely (all the Arks do), so isn't limited to by that. And the PCs then discover that the Ark they have is capable of manufacturing small mass relays - this was actually something hinted at in Mass Effect Andromeda, but wasn't actually a capability of those Arks. So this is when the real open-ended campaign would start, as the PCs can essentially travel around the galaxy (not excessively quickly, at maximum speed in a straight line IIRC it would take about two years to go edge-to-edge across the galaxy, for reference, and realistically you'd have to go around the galactic core etc. - the Mass Relays obviated this by acting as "jump gates", essentially), and spend time in places helping out and sometimes setting up small Mass Relays, so we could have an essentially limitless number of adventures around the war-wrecked galaxy, fixing things. The Ark could also reach systems which were essentially unexplored even before this because they were out of range of the normal drives and not near Mass Relays. Because the Ark is a big ship, too, it would have potentially had a lot of crewmembers and areas and so on. I was looking at Deep Space 9, the good bits of TNG/Voyager, Stargate: Universe, and so on for inspiration.
Anyway, I had way more detail than that, and still do, and that is easily the most-planned, most in-depth campaign I've ever created and was more interesting to me than almost any pre-written campaign. I still might be able to run it, but I really wish Mr ME-hater didn't hate ME so much because he's one of the key people in our main group.