Assuming you have a FireWire drive named FireWireDrive, open a Terminal and type:
$ cd /
$ mkdir /Volumes/FireWireDrive/opt
$ ln -s /Volumes/FireWireDrive/opt opt/
Then, install the DarwinPorts package installer. When you want to install other apps, simply type:
$ /opt/local/bin/port install application_name
The install will then place the app on the FireWire drive, not the internal drive. You'll not notice any difference in speed, etc. Now I have 100GB of space for X11 apps!
[robg adds: I haven't tested this one, but it makes sense -- there's no reason that symbolic links shouldn't work...]

