Is there any Nagios monitoring in place or is there the need to have some external reliability monitoring in place?
There is no external monitoring in place that I know of. I know ZC had some monitoring that was supposed to send me an email, but that was setup a few years ago, and recently didn't report the downtime.
My own mirroring reported the downtime (indirectly, by reporting that it couldn't mirror anymore); this is how I noticed one of the recent outages.
I can set up a Nagios machine to check the HTTP status of PyPi.
If it's easy to setup: why not? What exactly would that check?
As you said, we may have the same problem in the future on all mirroring nodes ...
Yes, there should be some more investigative work be done on the reason of the apparent unreliability.
The pep381mirror software produces a set of static files on the mirror, so you don't need to run PyPI itself. I merely use Apache to serve the PyPI mirrors.