It involved all the Scoobies (except Willow) being transmuted to the opposite gender. Buffy and Tara and Anya became boys, Spike and Xander became girls. Still in their own bodies, just new genders. Joyce was still alive, Buffy was with Riley and Xander and Anya were together. I'm 99% sure the Spander came in the form of a threesome with Anya, but I'm not definite on that bit. However, I'm fairly confident it was Spander because I've never read any other gender switch pairing fics besides Spander.
Hopefully, someone will be able to help! Naturally, as soon as I see the title, I'll be facepalming myself and thinking "Of course, it's [fill in the blank]! How could I have forgotten?" Thanks in advance, guys!