El Goonish Shive is a webcomic focusing on anime-like adventures, mild furry themes, and strong transgender/queer themes.
The plot is long and complicated, but basically a group of teenagers find themselves dealing with giant ooze monsters, mutants, magic anime powers, magic non-anime powers, alternate dimensions, and aliens. Some of these teens are mutants, clones, and/or/but/then magicians. But for the most part everything is going quite well, and at least half of the comic is more focused on teenagers, relationships, and geeky technical discussions of the in-world magic system. The magic is needlessly complex, and explaining the ins and outs often involves breaking the fourth wall, behind which there is another web-comic populated by a small set of characters whose only purpose in life is to explain the technical details of El Goonish Shive and engage in some mild innuendo.
As may already be apparent, the comic's author, Dan Shive, has a tendency to over-explain things. He also likes to use more words where less would do, and to cover the same concepts over and over again. On top of this, there is a extensive cast of characters, each of which appears in both male and female forms, each of which has alternate forms in alternate dimensions, and some of which have animal forms and/or magical disguises. This can make it hard to keep track of who is who. And moreover, this comic started in 2002 and is still going, now nearing its 2000th page. As the comic forms a single cohesive narrative, the whole thing works best if you start at the beginning.
Sounds awful, doesn't it? Well, it's a bit overwhelming, but it is also a lot of fun, pleasingly complex, and light enough that if you lose the thread of the plot every so often it's not that big a deal. It is probably a bit more interesting if you identify as a geek or genderqueer, but if you like aliens, magic, and careful analysis of feelings, social situations, and society in general, you will probably enjoy this comic.
Given the massive number of pages and the fact that the earlier comics are more cluttered and poorly drawn, you could hypothetically start at installment 858, just after a lot of complicated and crazy stuff happened, and alien hybrid Grace and newly created magical transgender clone Ellen are about to start on their first day of school, ever. You might also start at 1061, a fairly good entry point, but good lord you will have missed a lot of background. But that's okay, if you like it you can always go back and ready the earlier comics. I did.