For me, the only files that I worked on are ascx and css files.
I didn't modify those xml files, and I got the result I want.
So I don't think you need to modify the xml files.
Hope this help.
The catalook skin is defined in xml files (itempane for product view, list view in card or list format, dashboard, search, ) , ascx files contains calls to engine that use xml files to create controls at runtime. Changing xmls files you can define the layout of mainly elements of catalook.
There are some exceptions that use directly ascx files (like bookingcalendar in rentable items).
The XML and ASCX files will do exactly the same. Only the 'blue' skin includes both file types but this is not necessary. The compact-grey includes XML files only. Other skins e.g. the blue-neutral skin includes ASCX files only. The skinning engine looks at first for an ASCX file e.g. itempane.ascx, if not found, then for an XML file e.g. itempane.xml and if it can also not be found, the internal default skin will be used. You can use any standard ascx editor to edit the ascx files. We use the ascx editor from Visual Studio NET. Some forum users recommend other editors in older posts.
You can more information in chapters: 'Module Skinning' and 'HTML / ASCX Skinning'