If the Registration URL that appears inside a Signup Confirmation Email is returning a 404 Error and you're also running the BuddyPress plugin, you may not have configured your BuddyPress Registration Pages.

You must configure the BuddyPress Registration pages by selecting the corresponding pages inside WordPress Dashboard Settings BuddyPress Pages. Note that BuddyPress automatically generates the content for these pages, so you can just create a blank page called "Register" and another one called "Activate" and then select them inside the BuddyPress configuration.