I've found that with every episode I feel nervous about going in, I'm comfortable and laughing as soon as it starts. The asexual episode worried me because I have asexual friends (two of which were in the following Irregular, hi Chaz), but the first reading made me go "Oh, THOSE asexuals". Size acceptance is a big (hurr) thing for me because I spent sixteen years being told I was unhealthy and needed to exercise more/go on a diet by doctors, when the truth was that I had an enzymatic disorder keeping me from digesting food properly--especially since I had to be hospitalized with an ovarian cyst the size of a chicken egg for them to take a second look at me and diagnosis me correctly. But as aforementioned, the fat activist episode made a clear distinction between being happy and healthy and being in denial, and the other weight-related episodes did the same thing, as well as pointing out the inherently dangerous, codependent dynamic of the feeder/gainer fetish.
Every time an F+ episode has focused on a community, it's focused on the worst of that community, and I think that's what sets it apart. It's also never truly mean-spirited, which I think a lot of people don't get about snark. The majority of the stuff you make fun of, you don't truly hate, it's just mockable and funny. There are exceptions, like RooshV, where you honestly want the guy locked up and eating live jellyfish for the rest of his life, but those are reasonable exceptions. If you're hurting people or facilitating people being hurt, it's not a roast, it's a point being made.