In order to block a site by URL, set the following rule parameters:

Action : Block
Direction : In/Out
Source : Your LAN Zone or individual IP
Remote - Host : www.something_or_other.com
Source Port : Any
Remote Port - A set of ports :80,443

Important: To make this rule work, move it ABOVE the default ALLOW-IN-ZONE-ANY-ANY rule.

If it was below this rule in the list, the named site would not be blocked because it would be a valid response to an originating request.
If the BLOCK rule is moved above the default rule, only the named site is blocked, other sites can still be accessed.

More relevant info at: http://forums.comodo.com/index.php/topic,822.0.html