The ntuser.dat file is the HKEY_CURRENT_USER hive of the registry.
Unless you know of specific application that have stored large amounts of
data in the user portion of the registry and that you're no longer using
those applications, I wouldn't recommend touching these.
You could create yourself a new account and/or profile and migrate stuff to
it, but you'll lose application settings that way. Beware of just copying a
fresh ntuser.dat file into your profile. Although you have have full
control to the file, the ntuser.dat file has registry permissions embedded
inside it (that can be modified using regedt32.exe). If you're going to
start copying profiles around, always use the "copy to" functionality in the
profiles dialogue and change the "permitted to use" field.
Of course, when mucking around with the registry, always make sure you have
a good backup or five.
Is your larger than average hive causing you a specific problem?
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