Pillars of Eternity is my current video game obsession. An obvious and worthy successor to BG/BG2. I particularly love the setting / world-building, and have been thinking about what a tabletop game set in that world would be like. One really cool thing about the game is that it only examines a small slice of the world, but gives you enough info about the other pieces of the setting that you'd have a nice basis on which to build.
Now, although I love the game's mechanics as well, there are quite a few things that are essentially artifacts of it being a video game, and not particularly integral to the game's story or the world's themes, so I'd throw those out. The main things that I would want to keep, that are *not* purely fluff but actually have mechanical implications, are as follows, in descending order of importance:
-Races and Classes
With the caveat that most of the classes I'd leave as-is in terms of mapping to their 5E equivalents. I don't care if the power sets don't match all that well; the concept is what matters. There are only two classes I'd need to design: Chanters and Ciphers.
Chanters I might make a Bard variant, since that's the obvious analogue. The issue with trying to do them 'as-is' in the video game is that combat in 5E tends not to last long enough to make their whole 'build up Phrases over time in order to cast spells' thing viable. I could see allowing them to chant two Phrases per round, though.
Ciphers I'd be inclined to keep pretty close to the video game: regular attacks build up your Focus, then you unleash it to use your class abilities (which are a mix of Psychic damage and Save-or-Sucks); those abilities get cooler at higher levels but blow more Focus to power. What I imagine would happen in practice in a TTRPG is that a Cipher character would alternate between building up Focus in one battle and then spending it in the next. A Cipher would almost certainly be Dex/Int MAD, but that's hardly a combination that would be a tough sell to players. (And if someone wanted to wade into melee instead, they could go Str/Int with Con tertiary.)
The tricky bit is that both of those new classes are completely non-Vancian, and thus can just go-go-go like the energizer bunny all day long. I might be tempted to make some of their stuff short-rest rechargeable, putting them more in line with Warlocks. But maybe not. Given that everyone needs to rest simply to avoid Exhaustion levels, it might not be a problem to have some classes whose interesting stuff simply doesn't need to be recharged, as long as it's not overpowered.
Designing new races in 5E is quick and easy, so making Orlans, Aumua, and Godlike shouldn't be a problem. The subraces of the latter ought to be fun!
-National origin, as well as Race/Class/Background, gives you some skills and/or stats.
Again, this is mostly a matter of drawing up a list--not too tough. One easy-peasy way to handle this would be to make national origin a mini-background, granting one Skill or Toolkit prof.
-PCs can mod their own magic items; relatedly, 'masterwork' items are a thing.
-Reputation as a real, trackable, key resource.
The faction stuff in the DMG seems like it would help with this. And creating good, interesting organizations is key to making any location in the PoE world really hum. Dunryd Row, the Dozens, the Crucible Knights, and the animancers are what make Defiance Bay such a cool city, after all.
-No XP for killing members of PC races. Ever.
I do XP weirdly in 5E anyway, but yeah.