I'm pretty sure I've mentioned this concept previously, but it popped into my head again recently so I figured I might as well reiterate...
So, playing Shadow of Mordor back in the day, I was of course completely enamored by the Nemesis system and its potential (and a tiny bit saddened by how the game at the time didn't really use/abuse it to the fullest, but I was still happy with what I got), and have wanted to see more of it.
Around the same time, I also got into playing the Early Access Man O' War: Corsair (which is a deeply flawed title, but I still got a good hundred hours out of it or so), and was spending a lot of time sailing around up and down the coastline of the old world.
And that's when it struck me... A piratical seafaring adventure, with the other captains being handled by the Nemesis system! Each with their own personalities, specialties, identifying traits... Forge friendships, be owed blood debts, make enemies, get ambushed by that mad bastard you could've sworn you'd marooned on an island with a pistol and one shot, be boarding a merchant vessel when PLAYER 3 ENTERS THE GAME and that Dutchman you double-crossed is back for a chat now that you're caught with your pants down, get haunted by that crazy-eyed dervish you've personally seen walk the plank, get shot, stabbed, burned, cast overboard with a weight around his boots and so much more, but he keeps coming back because he's NOT FINISHED WITH YOU YET, BOY.
I just thought that the setting would lend itself quite well to the usage of that system... They'd use particular weapons/tactics, have an abundance of situations and interactions to display their quirks in, could even have their own personal flags! Imagine sailing alongside some random ship when a crewman shouts out that they're changing colors, and sure enough... It's that flag. That damned flag. You really thought you'd seen the last of her, and now? Right as you're limping back from a rough (but very lucrative) run? You sigh, groan, grit your teeth, and prepare for another life-or-death spat with that lady captain you're damned certain the devil himself sent to sea for the explicit purpose of showing you Hell before your time.
...and just when it's looking bad, a broadside cleaves into the she-demon's ship and you hear a familiar voice bellowing from the side of the cutter that's just come alongside: "THIS MAKES US EVEN, SWAB!", and you look over to see the leathery beard-ringed face of that slightly barmy fellow you took mercy on and rescued from being marooned on that sandbar a while back.
So, uh... Yeah. I just figured it worked with the system.