All right so ClickOnce seems to work again: publishing works. But when I try to launch a published program, it gives me a deployment error: "general activation failure".
Lucky me, it mentions "See the log file for more details". Unfortunately, it doesn't provide a hint as to what log file that is, or where I could find it. So far for extra credit on the "useful errormessages" department - but I remind myself that it's alpha software so I'm not complaining 
So I just reverted to the IIS logs, and it seems that the browser is trying to fetch a .manifest file for which it gets an HTTP/404 error.
Adding a new MIME type (.manifest, type text/xml) in IIS seems to do the trick, but I do suppose (i.e. hope) that this works by default on a clean box. So I'm just assuming that it's my setup (which is probably pretty messed up by now, cyclic installations of older and newer builds of various programs can't be too good).