I think you lose some of the navigation bits and pieces - obviously the large moving map (though you can put a small one up still), and I think possibly the ability to create / edit a flightplan (though direct to still works), but if you're not needing those then I don't see any problem.
You certainly wouldn't want to do it IFR as I think you lose the ability to select approaches etc.
The only other thing that comes to mind is you probably can't use the leaning guidance etc, but if you're doing this in the cruise then you've likely already leaned any way...