I have a extra PC with an intel i7 and GeForce GTX 1080 Ti.
My goal is a headless PMS that is always on and reliable and low maintenance, like I already enjoy from my QNAP TS-853A, but with more horsepower to transcode 1 or 2 streams of 4K HEVC for remote use and a wide range of player clients.
Recommendations on what distro to use? How to make sure hardware transcoding and the GPU is supported? How to properly connect it to the NAS with all the media?
Q1: how familiar are you with Linux 
A bit more than the basics. Enough to maintain pihole on a raspberry pi, and some light development work on Ubuntu. But not familiar with drivers and making sure the intel CPU and GPU are available to PMS etc. and have always had a challenge mounting a NAS without having the credentials stored in plaintext.
If you have a spare machine you might think about running unraid and then run plex in a docker container. That is what I run and is easy to work with and then you can use the Unraid as your nas.
I7 is mostly meaningless, what matters is the generation or model # like 3xxx or 7xxxx or whatever.
But to answer your question, if new Linux user best to stick with most recent LTS (long term service) Ubuntu.
This would likely provide the best balance of stability, good support for a wide variety of old and newer hardware, and new user friendliness.
Until you learn how to effectively remotely manage a Linux box, you should just run the default desktop with monitor/keyboard/mouse.
As far as learning Linux basics, google is probably your first and last stops.
oh… and of course there’s always some posts in the tips & tricks section w/ regards to some of the more tricky elements (e.g. how not to mount your drive so Plex gets a chance to see your media) 
This spare machine is an i7-5820K with 16GB and GTX 1080.
Not sure what unraid would offer here if I have no reason to retire the existing QNAP NAS.
Those Linux Tips have some of the answers I was already looking for, thanks for pointing that out.
Perhaps I should start with the most basic question: what OS to run PMS on given this spare machine. Given PMS as the only use case, and ignoring the cost of Windows, what are the pros and cons? As a reliable, headless server, I just thought of linux. But will I be able to get the most (e.g. transcode) performance out of it from one OS vs the other?
Personally I’d go for the Linux. The question is then what distribution to use… if you ask 10 people, you’ll probably get 15 preferences for that
I’ve opted for a Ubuntu system. As per TechnoJunky’s point, I’ve installed a LTS version (currently 20.04). That being said… others will have good reasons for opting for other distros.
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