I've seen quite a few ideas on here about changing / implementing different shortcuts that are more in line with different OS's paradigms (OSX, etc).
I'm not sure how hard this would be to implement (I'm not familiar with how Gnome's configuration is set - if everything is settable programmaticaly, it shouldn't be too hard), but it seems to me that a good solution would be to ask the user during installation whether they are a first-time linux user, and if so what OS they were using previously, and to modify keyboard and mouse shortcuts accordingly.
I'm assuming that this could be done for keyboard shortcuts for the desktop environment, and probably for mouse behaviour as well. Other OS-specific features (like drag a cd into the trash to unmount it) would probably be more of a hassle to implement.
Add some sort of notification on first run telling the user about this, and how to modify the settings - plus maybe alert them to some helpful features they might not have had before (for instance, if someone was coming from Windows, they probably wouldn't know about middle-mouse cut and paste).