I'd use something like Danga::Socket and write an event-based system. There's already an http server or two (perlbal, mogstored) written using Danga::Socket it which you could modify or take chunks from.

I think you can add non-socket fds into the event loop (see the OtherFds method) so you can look for events on your watched files too.

I guess POE is always a popular suggestion too, although I've not used it.