The only downsides I've found are:

(1) it's more of a pain to try out modules that may or may not be PowerPC friendly, since so much code out there is developed on x86 architecture. CPAN works but doesn't manage package installations and dependencies like Fink would, and Fink rarely lists the perl package you want.

(2) you can't use generic shebang scripts as Speakable Items and probably some other carryovers from pre-OSX days. You have to wrap each one with a little AppleScript stub instead. There are easy programs to make those stubs, like Platypus.

I haven't tried Gtk2::* packages on OSX though. If someone else lets me know how that works out, I'd like to know.