Hello,
The following is untested theoretical code. But it may very well work without a problem.
Assuming that you may do this kind of thing based on other parameters such as product, company, etc., you will create a page specifically as a "router" for username queries. We'll create a directory called user/ and make its index page our router.
Since you want to have a URL like http://mysite.com/user/msmith translate into http://mysite.com?user=msmith, you will first parse out the username portion of the URL. To do this, use a combination of substr and strrpos.
$user = substr($REQUEST_URI, strrpos("/", $REQUEST_URI));
This should grab the username from the end of your url.
Now you simply have to use a Header redirect to send them to the appropriate page with the appropriate querystring in place.
header ("Location: /index.php?user=msmith");
I hope that is something similar to the solution you are looking for.