The best way to organize your Mac is this:
1. One partition for the system folder only (OS). It should take 1G at list and I think is enough (I do not run OS yet, this is for clasic system).
2. A secund partition with all the software (Soft), usually from 2G to 3G. My folders are sub devided like this:
-Audio (Protools, Digital Performer, iTunes, etc)
-Video&Animation (After Effects, Final Cut Pro, etc)
-Publishing (Photoshop, Illustrator, Omnipage Pro, Office)
-Tools (Hackers helper, Norton, Toast, etc)
-Web (Dreamweaver, Flash, Hotline, Limewire, etc)
-VJ (Arkaos, Rithmic Circle Fuse, Artmatic, etc)
3. A third partition called Storage. There is where you are gonna place all your text files, pictures, movies, downloads, etc.
In that way you will resolve the followed problems:
1. Fragmentation caused by the used of files preventing from alter the OS or the softwares making your computer more stable.
2. Easy acces to your files, specially if you create an alias of the "soft" partition and place it on the Apple menu items.
3. Viruses would get stock in one partition in case they appear, living the rest of the computer alone.
A very good trick that I discovered recently and is keeping my desk clean is this:
1.Create one file with the Simple Text.
2.Place it in the Apple menu items with a name that start with "Z" or "X" to be placed at the botton of the menu.
3.Now, every time you have to write something down (e-mail, phone numbers, name, note, etc) you are gonna do it there in place of using the crappy stickers or a piece of paper that eventually will get lost.
The beauty of this is that, that file would be easy to find because would be at the end of the Apple menu items. Then you will have to save it (stickers get deleted easilly) and is the easiest way to keep track of your notes of the week. And the file opens very fast because the Simple Text is very light.
My bigest problem is that I'm always writing something down and I run out of paper, and then I write on the back, on the borders, etc... and later I lost the paper between the 30 others I had before. Now my desk is clean
These are the best tricks to optimize my work on my Mac.