I think it’s really a matter of personal preference, as well as the type of content on your site. Personally, when setting up directories, I like to start with general folders, with more specific folders inside, to keep things easier to manage. For example, I might set up an images folder like this:
images/
images/global/ (background images referenced in css, logos, etc. stuff that appears on every page)
images/gallery/
images/gallery/batch
images/gallery/thumbs/
images/gallery/medium/
images/gallery/large/
images/posts/ (random images in weblog entries, etc.)
I also like to create a “files” directory when I’m going to have pdfs or something available to download. Within that directory, I’ll add sub-folders based on the contents. I don’t like the “uploads” title, because, although I’m uploading a file to it from the control panel, someone else may be downloading the file from the site, so telling someone to download a pdf from my uploads seems strange to me.
My general preference is for more folders/hierarchy than is probably absolutely necessary, but I try to avoid having files and folders mixed in a single directory, since it gets difficult to keep track of things when everything is randomly dumped into a single folder.
That said, however, I tend to leave the folders that are created in the default EE installation alone, simply because I don’t want to spend the time tracking down all of the paths and settings in the control panel to update them to a customized system.