WP doesn't seem to validate the uniqueness of a generated user_nicename upon registration, which can result in duplicates (ie. if someone registers with username "superann" and another person registers with "super.ann" I believe they sanitize to the same thing). Since the nicenames aren't unique, this can create a problem if you're calling up anything keyed off the user_nicename, such as an author page. Since user_nicename is auto-generated (and should be fixed to generate a unique key) but still likely a visible field, my preference would be for this to be a settable option for users in their profile options.
Also, the registration functions won't allow a duplicate email address by default, but if you're logged in on your profile and change the email to one that's already in the database for another user, it does no checking and simply allows the change to be saved. This seems inconsistent and my preference would be for the admin to be able to set whether they allow or disallow duplicate email addresses upon registration, and have that setting be consistent with whatever the constraints are for a user being able to change their email address in their profile afterwards.
I was also thinking that email addresses shouldn't be allowed as a username, OR if it is allowed it should be consistent with whatever the user's actual email address is (so auto updated whenever the user's email address changes). Otherwise it gets really weird if a user can have a username that is an actual email address but isn't their email address!
While I'm at it let me throw in my vote for allowing users to log in by email instead of (or in addition to?) username, too.