First of all, follow the principle of collection buckets: Use as many as you need to but as few as you can get away with. So, for me, my ~/Documents/School folder has several subdirectories for individual classes, but I can get away with fewer. ~/Documents/Web Design, however, has subdirectories for Wordpress, Drupal, and individual projects, because I don't want all of it getting jumbled up. I can't get away with fewer there.

I don't recommend the dump-it-all-in-one-directory option. Spotlight, Quicksilver, and others are really great tools, but one of these days you will have to go digging for that doc, and woe be unto you when you do! Usually, life will have several spheres that are natural grouping elements. I say create a folder for each major area of your life and then use tags, etc. to get the fine grain organization you are after.

Also, I always create a directory that serves as a collection bucket for downloads. Mine is at ~/Downloads (brilliant!). Some people use their desktops for downloads, but I hate my desktop to be cluttered. This serves as a processing stage for your downloads. You look at that disk image of that app you tried and hated, and you immediately say, "Rubbish!" and toss it in Trash. This is extremely helpful for me.

I doubt you are starting over with all new files as well, but it couldn't hurt to come up with a handy taxonomy for your filenames. For instance, in my School directories I name my files with the kind of document it is "paper," "reference," "syllabus," whatever followed by usually the professor's last name if applicable "Balch" and then an appropriate filename. All these are separated by dashes. So, my syllabus for this semester's class on Romans might look something like this: syllabus-balch-romans.doc Sometimes, if I think it necessary, I will include the term as well. So, syllabus-spring2006-balch-romans.doc. It's a bit of a toss-up where the term goes, because I have two classes with Balch this semester and I have had more than five with him overall. But, either way you slice it, it works pretty well. Then you can do your SmartFolders by "Filename contains: Spring2006" etc. and this is another way to do metadata.

If you are starting from a fresh install of OS X, I can't recommend AppZapper enough. Over time, your /Library and ~/Library folders will get clogged up with junk prefs and support files from apps you haven't used since God was a child. AppZapper gets rid of everything associated with an app when you want to delete it. I'm not affiliated with them in any other way than a happy user of the software. (That might have something to do with the fact that I got it for free over at MacZot a while back.)

Wow, that was long, but I hope it helps anyway.