The GNOME desktop is an infinitely customisable environment. The
Desktop > Preferences menu provides the means to adjust the most commonly used settings. Here follow some suggestions on how to tweak GNOME appropriately for your own needs.
Accessibility

You can configure assistive technology support such as the Gnome Screen reader, Magnifier or On-screen Keyboard, should they be required. You will need to log out and back in before these changes will take effect.
About Me

Fill in personal details. Most importantly, this dialog allows you to change your password if necessary.
CD Database Server
Configure the system to look-up and submit CD track listings.
Desktop Background

You can choose one of the supplied images or import one of your own. The dialog allows you have the image fill the screen, centred, scaled, zoom or tiled as you choose. You can also choose to have a plain colour instead.
The process of creating a new desktop background is simple, just create a new folder called 'wallpapers' or something similar and save appropriate artwork into that. You can make wallpapers yourself quite easily using one of the graphics applications.
File Management

Configure the behaviour of nautilus, the file browser. Nautilus also controls the look and behaviour of your Desktop.
File Associations can be controlled by selecting Right-click > Properties from the File Icon's context menu. The Open With tab controls file associations and the Permissions tab controls, erm, permissions. So long as you own the file you should be able to edit as you see fit.
Files with names beginning with a dot (period) are hidden by default. Tick View > Show Hidden Files in order to view them with the file browser.
Font

Choose which fonts are used to display things on the desktop. Some users find larger fonts or a different style such as serif can make on-screen reading easier.
If you don't like the initial font selection in 64 Studio, you can get more fonts from the main Debian repositories. Search for "fonts" using the Search facility in Synaptic. Look for packages starting with "ttf" or "xfonts", there should be plenty to choose from.
Keyboard

Configure keyboard behaviour to suit your needs.
Keyboard Shortcuts (Hotkeys)

Many functions can be called using key combinations, as in other operating systems. Linux's equivalent of 'hotkeys' are called keybindings: there are two main conflicting standards - A sort of Windowsy one and the GNU-emacs standard (all that C-x C-c stuff you keep seeing) The good thing is you can usually define your own.
Login photo

You can drag an appropriate image of yourself to be used on the GDM login screen. You need to use a theme that displays a list of users for this to work.
Menus & Toolbars

Configure the behaviour of Menus and Toolbars on a simple level.
Mouse

Configure the mouse for left handed use, pointer themes etc.
Multimedia systems selector
Define the default plugins to use to play Audio and Video. You shouldn't have to mess with this.
Network Proxy

If you don't know what one of these is, you probably don't need it right now. Your network administrator may require you to use a proxy to access the internet, if direct connections are disallowed.
Preferred Applications

Allows you to specify which Web browser, mail client and terminal application you want to use as default. For greater control over default applications, you need to use the command-line
# update-alternatives --all
This will take you through all the application types that have multiple posibilities and offer you the choice. If you don't know or care, you can press enter to choose the existing default.
Removable Drives and Media

Configure how the system deals with external drives and devices, like digital cameras, removable storage devices, PDAs, printers, scanners and the like.
Screen resolution

Adjust the screen resolution from your desktop.
Screensaver

Choose screensaver themes and fine tune them. You can choose whether to lock the screen when the screensaver activates, this forces you to enter a password when you return to your computer before you are allowed back into your Desktop. It's enabled by default, but only really useful in multi-user situations.
Sessions

This allows you to save your session. Whatever applications you have open now will start up the next time you log in. You can manage your Current Session in the middle tab. Select any applications that you don't want to start up by default and click on the Remove. When you are happy with the list you have left click on Apply. You can configure which applications you do want to open up by default the next time you log in, by adding them to the list in the Startup Programs tab. Once you're satisfied with your choices you can click on the Save the current session button in the Session Options tab.
Sounds

Enables you to choose audible alerts and ear-candy themes. This is disabled by default in 64 Studio.
Theme

New themes can be installed using Synaptic; go to Sections > GNOME Desktop Environment and select gnome-themes-extras for installation or choose one of the gtk2-engines-* packages. Alternatively there are lots of themes available online (see links below).
Themes, Icons and window borders can be installed by dragging and dropping them onto the theme manager.
It is possible to create custom themes by mixing and matching theme, icon and window border sets and it is also possible to edit your gtkrc file and make custom pixmap textures to create further variations.
Volume control

The default mixer for the audio system. File > Change Device allows you to switch between audio devices if you have more than one attached to your machine. Edit > Preferences controls which channels are visible.
Windows

Hold down the ALT key whilst dragging with the mouse to move windows around.
The behaviour of windows can be further modified in
Desktop > Preferences > Windows.
links
Accessibility
GNOME 2.14 Desktop Accessibility Guide
Linux Accessibility HOWTO
Desktop Themes:
http://art.gnome.org/
http://www.gnome-look.org/