Sharepoint - Modification of '_layouts/upload.aspx'

One method I've used to customize the upload page is to take a copy of upload.aspx and rename it to something like upload2.aspx. Keep it in the /layouts folder (or subfolder of) since it won't like being anywhere else.

Once you have the copy, you can make your modifications as you like.

The last step is to tell the upload menu items on the document library toolbars to point to the new upload page. You can do this with some jQuery, for example

$("ie\\:menuitem[text='Upload Document']").each(function(){

   $(this).attr('onMenuClick', $(this).attr('onMenuClick')
          .replace('Upload.aspx', 'Upload2.aspx'));
 });

I've been asked to do this, too, and there's no really good answer that I've come up with. If you hack the _layouts/upload.aspx page, it'll take effect throughout the Site Collection(s) on that WFE. (And you will no longer be in a "supported state", and an upgrade will clobber it, and hair will grow out of your palms.)

You can, however, create a customized upload.aspx for a specific list by cloning the page and changing the New Document Form in Supporting Files for that list.