Fwiw, I just abandoned Lemmy in favor of PieFed. It allows you to block whatever custom instance you want - in my case Lemmy.ml - it has “categories” of communities so you don’t have to browse on All, it has a “reputation” feature that puts icons next to users doing patterns of extremely obvious trolling (like a <1-month old account with negative karma - note that such are not “banned”, merely “labelled”, so that you can make your own determination of what to do or not about such), and it has a fairly polished interface. It has its quirks, like searching for a user is different than searching for posts, but it keeps improving all the time and the developers are extremely receptive to feedback.

Unlike Lemmy, where 0.19 was supposed to allow user filtering of instances, but what was delivered in 0.19.3 fell far short of desires, then 0.19.5 rolled back what little protections had been previously offered. At this point I don’t think you’ll ever be able to block all users from lemmy.ml, so long as you remain where you are. Lemmy.world admins could do it, but it seems highly doubtful so long as certain communities such as !Firefox@lemmy.ml are located there.

Lemmy.cafe and Tesseract on dubvee.org have defederated from lemmy.ml though. And maybe some apps allows user-level defederation I dunno. So those seem to be your options - which aren’t a lot but at least they exist!:-)

kbin has a few extra bells and whistles, like it can also do mastodon-style “microblogging” and custom themes per user. it’s since ceased developement but mbin is a fork continuing it. other than that, the experience is the same