I want to say upfront that I have no problem with obscure jokes, about any subject. If every XKCD was like this, it could carve out a nice niche in the side of the Internet we’d never bother each other again. The problem comes when the material is split between accessible material and things like this. I’d say by this point, most XKCDs could be considered widely accessible (note: “accessible” and “good” are two separate categories). And then Randy throws out something like this.
I want to compare this to Irregular Webcomic, which uses science jokes somewhat more regularly, so you understand what you’re getting into. However, every time the author (I’ll call him David Morgan Mar, ‘cause that’s his name) uses an obscure science joke, he uses the annotation to explain the science and such. This is also used as another opportunity to make jokes. That’s good because it doesn’t make you look for the punchline, and if you didn’t get the first one you can get the next.
Compare both of these to QI and Saturday Morning Breakfast Cereal, which tell you information and then make jokes about it. See, that’s the best way because it educates you as the setup, then tells you the punchline. XKCD tells you a punchline and then makes you look up the setup, which has never been funny and will never be funny.