Is there a good guide or way to tell which side content is worthwhile and what is busywork?
Marked sidequests, character quests, tales of greece usually often have some story elements to them and will often take you to unique places. I think these all have an exclamation mark on the map. They're kinda all worth it. Most every island will have its own quest chains associated with it. The game has 2 other major main quest prongs in addition to the main story -- the assassinations, and the mythology which you need to explore for find out, though in the process of the main quest you make some headway into them iirc. There's also the nemesis system-ish mercenary stuff which is good and ties into various quest arcs on some islands.
The stuff like clearing bandit camps, nation power battles etc. is far more skippable.
It's an absolutely massive game, with a density of meaningful content up there with something like Witcher 3, even if sometimes the writing isn't quite as good.
Also turn down level scaling if you want to have an easier time.