This exact same thing happened to me yesterday, Win7, Calibre 4.23 (I've been hanging onto this old version because it has the DRM remover and I've gotten very confused about the new ones/replacements). I came back from vacation to download my latest fanfic chapter updates via FanficFare, and Calibre had NONE of my plugins in any of the menus. But the Preferences says they're all installed. The books/fanfics all appear to be present, though it's hard to say given there's so many of them.
I'm pre-emptively copying all the Roaming/AppData files and the entire Calibre Library to an extra external drive I had handy, but uh...is there a way to get this working on my computer again?