Over the last few years I've noticed that some videos will be unable to buffer while play, some will easily keep up/avoid pauses during play, and some can take 5-10 minutes to pre-buffer before its a reliable viewing experience and others? 30 seconds.

I'm running a Ryzen 5 5600x, a 4070, 32 GB of ram, and I'm on fiber internet. No other sites usually have a buffering problem, and even on E621 some videos are 4k and fine while others can be 720 or even 1080p and struggle. Its not uncommon for me to have to wait for a few minutes for a video to prebuffer after pressing play then pausing before I can reliably watch it without hitches until the end. And this is the case with being the only E621 tab up or 5, whether only one is actively loading or all 5, or if its 10 or w/e.

Neither CPU nor GPU nor RAM come anywhere even close to 60-80% usage, let alone 100%, so I cannot imagine there is a problem there.
Is this a known issue with Chrome and I should hop my e621 needs to another browser? Is there a reason/way to identify the cause of the buffering?
Is this just a known problem with how some folks files are uploaded/managed?

I use chrome and all of my videos load instantly, so I doubt it's a browser issue unless yours is outdated, or you have a bunch of extensions. It could also be possible that your ISP.

try opening the site with a different browser or your normal browser in a safe mode window (or whatever the chrome equivalent to that is), if the problem persists then the bottleneck is potentially your computer or, more likely, something even further upstream.

I highly doubt hardware has anything to do with it, I can watch 4K videos on an iGPU of an i5 with no problem. This sounds more like a software problem, I would try clearing the sites cache and/or cookies to see if it helps, you could also try using a VPN/Tor to see if anything changes, it could be your ISP, your browser or even firewall.