Setting up for external drive

I am just beginning to use Blender and thought it best to ask now and avoid frustrations later. I would like to use a 1TB external drive that I have for my files. (I have a laptop and I do not want to overload the HDD on it. I also want to be able to switch to a desktop for rendering video sequences so that I do not tie up my laptop.) With other video editing programs I have used, I have organized all of the files into directories under that program’s name on the external hard drive and this has reduced future confusion. I have installed Blender 2.49 and Python. What is the best way to configure Blender for use of an external HDD. (I am open to several opinions on this.) What setting do I change? What files do I move, where are they by default and how should I configure them on the external HDD?

One option I am investigating is using the PortableApps version of Blender and Python and simply running them from the HDD. Any down sides to this that anyone can foresee?

Please keep in mind that I am a newbee.

System Information:
Windows XP SP3 laptop
Windows Vista Desktop