I got chance to play again today and now know why it's behaving like it is, but I don't understand it.
If I aim the Harmony directly at the box, which is under the TV, then it will practically ignore all commands. However if I point the remote away from the NUC, at the wall, ceiling, etc. then every time the IR signal gets to the NUC and XBMC works and moves through the menus.
Very odd, but it works a treat now.
The NUC is sleeping well and recovering into XBMC without issue. It's all setup on the Harmony activities. Only issue I did have is after a full reboot if XBMC is launched as a startup command then it won't see my library correctly. I've dropped the launch to a batch file with a 8 sec delay and that's sorted it all out now.
Just need to figure a way around the XBox turning on now and the NUC will be my best buy this year...