Yep, the easiest way is to just load the config file into an XMLDocument object, make whatever changes you need, then save it back out. The changes will take effect the next time the app starts.
With XMLDocument, you can add, update, and delete items wherever you need to in the configuration. Pretty straightforward really, as long as you know how to use the System.Xml namespace.
There's also a configuration application block you can use. And you can use custom configuration sections, which is cool but may be overkill.
I'm not sure what you mean by using XML serialization. That's a way of persisting objects as XML.
Don |