Do not delete the .android_secure folder or any "." folder that belongs to an application still installed on the phone.
Do not delete the Android folder
Do not delete and folders that are even remotely named like an app you have installed. If it's an app you uninstalled, then you can delete it.
As a general rule of thumb, copy everything to a folder on your computer, then delete the extra nandroids, rom downloads, and folders that you don't want. If you delete something important, you can always restore it from your copy.
When in doubt, back it up before deleting!
Hope this helps.