It really depends on what you need to do with your app. If it's a heavy use site, you will have a hard time competing with apache and cgi(mod_perl) for performance reasons.

But if it is a custom low use app, a Perl Tk or Gtk2 gui can be quite useful. It can run without a constant server going. It can use many different ports. It can use better encryption than the 128-bit web stuff. etc. etc.

If you go the roll-your-own route, the big problem is setting a protocol for you to use, and serializing data (so you can send hashes over the net).

The Net::EasyTCP makes this pretty easy. I have a demo at ztk-enchat encrypted server client