I run umatrix, and I block everything. Cookies, CSS, images, scripts, media, XHR, etc. Everything, except for CSS and images from the thirst-party domain (e.g. *.ycombinator.com).
Most sites actually work better with this. They're faster, there's less clutter, no ads, less risk. Some need a little convincing by unblocking some CSS or images. Umatrix makes this super easy. If a site requires javascript to run, I just skip that content. It's different for web apps like trello or github of course. Those get much more permissions.
> How on earth do you navigate what to let through and what to block?
umatrix gives a nice matrix (duh) that shows exactly what's trying to load. I dont often need to unblock things, but when I do, it's usually obvious right away. Takes maybe two clicks. Worth the effort IMHO