|laziness, impatience, and hubris
I've found that PREFIX alone is sometimes not enough. HTML::Mason, for example, would not install for me without all the added info. Here's the setup I use when I run perl Makefile.PL:
I have this saved in a file called popt (for perl options) and I just issue the command perl Makefile.PL `cat ~/popt`. I like to recreate the /usr hierarchy of a traditional perl installation, but that is not necessary.
To add modules to your search path you have a couple of options. You may be able to modify the enviroment on your server through an .htaccess file (if you are on an apache based system). On a mod_perl enabled server, you can use PerlSetEnv PERL5LIB /path/to/private/libraries/. Otherwise you are likely to be stuck adding a use lib qw(/path/to/modules /ya/path/to/modules); to each script.