When I upgraded to Mac OS X 10.5 with Time Machine and Boot Camp I found my 160GB Lacie mini hard drive was suddenly running short on space so I decided to investigate how difficult it would be to replace the hard drive. It turns out it is quite simple. I have a 160GB Firewire model without the hub. Hub models may have a bit more wires going over the drive to contend with. To open the case the four rubber feet in each corner must be removed to expose four philips head screws. Unscrew these, then lift the metal bottom of the case off towards the back where the ports are.
You will now see the underside of the hard drive with the IDE ribbon cable and power going over the drive. There are four philips head screws securing the hard drive. The two screws facing the ports and the back of the drive are easy to access.
The other two, however must be removed by lifting up the top of the case (turning the enclosure upside down can facilitate this). Be careful not to break the cable leading to the LED.
The drive is now free to be unplugged and replaced. At least in my 160GB model the drive was a Western Digital Caviar. Remember when buying a replacement drive that the enclosure has an IDE controller and SATA drives will not work. This is a shame as high capacity IDE drives tend to cost quite a bit more than their SATA counterparts. Once you have swapped the power and IDE cables onto the new drive you can reverse the process to reassemble the enclosure.
Once the drive is put back together you can put the feet back on with super glue or a similar glue. Congratulations, now all that's left is to partition and format the drive. Assuming you are using MAC OS X, go to Applications > Utilities > and open Disk Utility to initialize the drive. I chose to partition mine to have half it's space free to install Windows applications and files for use with Bootcamp.