Ahem. I stand corrected. Epilogue is a much better word for it.
Has Rich actually mentioned anything about 666 being a special strip, or is that just an assumption that is being made?
It's just an assumption. Usually Rich marks the anniversary strips with a dramatic transition that indicates the wrapping up of an existing subplot or the start of a new one. Sometimes he subverts expectations and doesn't.
#50: The Semi-Secret Origin of Elan and Nale.
#100:
Subverted, nothing special.
#200: Miko's big reveal.
#300: Splash page of Xykon's army, revelation that they're heading for Azure City.
#400: Haley and Elan's first kiss.
#500: Roy taking up observation of the mortal world.
#600:
Subverted, nothing special. Shout-out to strip #100.
#666 isn't an anniversary per se, but it is a number with dramatic/cultural significance. (Especially among D&D players, seeing as how we all worship Satan and practice black magic... yeah.) And with the OotS being reunited and everything clearly moving toward one of those big transitional moments, expectations are high.
Edit: Also worth noting, we are almost certainly nearing the end of the next OotS book. IIRC, "Dungeon Crawling Fools" was 121 strips long, not counting bonus material. "No Cure For The Paladin Blues" was longer, clocking in at 179 (strips 122 to 300). "War and XPs" was similar at 184 (strips 301 to 484). If Rich wraps up on strip 666, then [insert name of next book here] will be 182 strips long, just about the same as the previous two.
Exact numbers may be a bit off; I don't have the books in front of me.