Simple as that, that's excactly what I want to do in my buddypress:
www.mydomain.com/[USER]/ so as it will direct to user's public profiles.
I have found this link but wasn't helpful to me http://wordpress.org/support/topic/plugin-theme-my-login-username-in-permalink
Here's an easier way:
Put profiles in the root — http://example.org/username/
define ( 'BP_ENABLE_ROOT_PROFILES', true );
This goes in your wp-content/plugins/bp-custom.php file If you don't have such a file, create one.
More info: http://codex.buddypress.org/extending-buddypress/changing-internal-configuration-settings/