Michael Schwern has started a fantastic page on the Perl 5 Wiki onbest practices for keeping your Perl installation sane and happy.
Some high-level excerpts:
First and foremost thing I can say is if you depend heavily on Perl (or any single piece of technology) build it yourself…. Second, if you do build your own Perl, leave the system Perl alone….. Third, isolate your perl installs so you can have many installed in parallel….
Well-written information from someone who knows, and since it’s a wiki, you can help add to it as well.