When you are editing the Network Options, the options are fairly explainable. However, I wanted to add a couple things to some of the items. First you deal with Operational Settings, which include Network Name and Network Admin Email. Both are self-explainatory; however, the Network Name is what appears when a new blog is started on the domain. For example, if I were to start myblog on mydomain.com, just as WordPress has "Another WordPress blog" (or whatever), your multi-site will say "Just another My Network Name Site" for mysite.mydomain.com.
Under Dashboard Settings, the Dashboard Site, which was somewhat confusing for me at first, will create a sub-site if you wish to use a separate site to administer your users. If left blank (which it will default to if you enter anything with a space), it will add all new users to mydomain.com. Personally, I would also change the admin notice feed to something else other than the main site feed, as it recommends. I would also create a Feedburner feed so if I ever decide to change or manipulate it, I am dealing with Feedburner, which has a lot more flexibility unless you want to create your own RSS feed.
Under Registration Settings, if you have Registration disabled for whatever reason, you'll notice that Multi-Site recommends "please set NOBLOGREDIRECT in wp-config.php to a URL you will redirect visitors to if they visit a non-existent site." What is this? How do I do this?
First the define NOBLOGREDIRECT redirects a person to your chosen URL if/when someone enters a subdomain/subdirectory that does not exist on your site. You could use this to go to a SEARCH page, a FAQ page, or some other custom page. If you do not use this, then when someone enters http://badsubdomain.mydomain.com (a site that does not exist), it would direct them to the SIGNUP page asking whether or not the visitor can create the bad subdomain in question. Here is a good explanation on the NOBLOGREDIRECT and 404s.
Second, open wp-config.php and add among the define additions the following:
[php]<strong>define('NOBLOGREDIRECT', '%siteurl%');</strong>[/php]
The rest is fairly self-explanatory. Enjoy!