I have been asked a few times what is the best way to set permission. Here is what I have discovered. Remember to use proper permissions when creating sub sites, lists, or libraries. The easiest way would be to let your Server Manager take care of your groups through Active Directory, which already should be created for email and network permissions. SharePoint will sync with single-sign on and access those groups. There are times when I want to create a quick custom group, then I'll create those groups within SharePoint, but for the most part, I only use AD groups.
Always use groups though, if you use single user permissions, in the long run you will regret it. If the user leaves or switches responsibilities, you only have to switch out users in the groups, not each individual permission you set. Groups are easier to keep organized and will save you a lot of time in the future.
One more thing, when creating target audiences, you can ONLY use SharePoint groups, AD groups won't work unless you install this hot fix from Microsoft.