Excluding the active bigots and abusers, I think my least favorite subjects are the fetishists who are fixated on coercing their uninterested partners into fulfilling their fetishes, or where it seems like a major part of the fetish is the coercion or tricking someone into participating. The hoop-earrings guys have been mentioned and are grotesque, but I also found the watch fetishists who were specifically into borrowing random women's watches to jack off with/on, and then return, to be really unpleasant. There was also the freeballer who was really into freeballing in bike shorts at the public library and positioning himself so that librarians had to stare at his crotch -- ugh.
For most likable, I'm generally okay with fetish episodes where there's clearly a community on both sides of a fetish mutually enjoying it, even though most of those episodes are about objectively weirder things; the recent macro/micro episode, for example, was easier listening for me than many because most of those topics were being participated in by enthusiastic consenting people, even if they were weirdos. I also have a soft spot for people who are clearly just very confused and/or kids, like a lot of the question-askers in the various episodes about Yahoo-Answers-type websites. Some people are just dumb teenagers who have urgent questions about pregnancy despite not being able to spell "pregnant," and I hope they muddle through.