Using Skype in TV mode on a Mac Mini
I have much the same setup as you and therefore ran into much the same dilemma, so the following may not answer your question, but it might help! 

I began by using Remote Buddy's "Virtual Mouse" function to use my Apple Remote to navigate around Skype using the directional buttons to move the mouse around (once contacts are set up, its mostly moving and clicking). However, I'm the first to admit this is a bit clunky and not exactly ideal. (I realise you're using a Harmony One, as opposed to an Apple Remote, which doesn't appear to be officially supported, but it looks as though its possible to pair it with Remote Buddy).

In the end, I gave in a bought a Logitech diNovo Mini which is good enough for when I need a keyboard and mouse. And you can also use it for some Couch-friendly surfing too :)