You can configure settings for layout, menus, headers and footers at either the SITE or SPACE level.
How do I know whether to configure these settings at the site or space level?
A good practice is to configure site-wide settings when you want Zen to populate them over a majority of the site. Configure any space-specific settings from within the space.
Generally speaking, you will see the same configurable settings for the site that you see in a space.