Don't get me wrong, I have every intention of getting an IR extender/Harmony. But the thing with those are:
1. If you're doing a long sequence you have to sit there pointing the remote at the device for a minute while it does change 1, then change 2, etc. A serial connection lets you queue multiple commands on the box.
2. If I have a mouse in my hand, I don't want to pick up a remote to do something I can do with a mouse
3. Icons > Remotes for people who don't know how a "complicated" remote works

At this point I don't know if there is anything more useful a computer can do than turning things on/off (well, more useful versus a remote), but if there are that is what I'm looking for. I'm sure people have hooked computers up to receivers before and done useful automation with them, I'm just surprised I'm not seeing anything come up here.

One example that I thought someone might suggest would be that - say - when you open a music player volume is set to a certain level and the audio output type is set correctly for you. You could do that with a remote, but you first have to open the program on the HTPC, then grab the remote, then hold the remote while it changes things for you... versus having a script that does it all for you. See what I mean?