Not wholly unrelated, but I have endless trouble running my full version of Melodyne as a 'Region FX'. The Region FX menu is often totally greyed out when in fact Melodyne is present, and I often find I can't 'deload' it, during which time I can't split, copy sections of the track.
 
I've resorted to loading as a track FX where it works sweet as a nut, like it always has. 

More unexplainable bizarreness - but before that, I want to emphasize from the perspective of the original post, Melodyne works fine in stand-alone as well as in most of my Sonar (Ipswich) projects .  This eliminates concerns about running as admin, hardware conflicts, etc.  If it were in those arenas it would fail always, not sometimes.
 
So the news: this morning I set about making a smaller version of the BadMelo project (one where Melodyne could only work normally if I fooled it by the "open GoodMelo first" trick) for shipment to Cake analysis.  After I stripped out everything in the synth rack, I saved with new name (BadMelo_01, as it happens) and tested that I still could not invoke Melodyne successfully - check, still broken - cool.  However, once I closed and re-opened BadMelo_01 suddenly Melodyne is happy and I get golden blobs.  F*&* !
 
This put me in "find the offending soft synth mode".  This is a tiresome place to be, because you repeatedly open the original problem project, remove one item, save, close, and open again - hopefully until you are able to associate one change in the project with a resolution of the initial problem.  Sadly, I could find no specific vst being absolutely identifiable as the culprit - any reduction in the number of vst synths created a situation where Melodyne would open properly (after save, close, reopen).  To make matters worse, after hours of fooling around with this, suddenly the original project was able to open with a functional Melodyne.
 
So (sidebar to Noel here) I can't reliably create a small bundle that exhibits the problem.
 
I now get a sneaking feeling that this may have something to do with a timeout of some sort on the Melodyne plug - like maybe in large projects where there is a bunch of "stuff", it can't do what it needs to do for validation quick enough and just throws in the towel, sorry kid, greyed-out mode for you.

Had this problem within the last couple months. The Cakewalk version of Melodyne got installed with
one of the monthly updates, and after that would only open in playback mode. I spent about an hour
on the phone with Cakewalk sorting this out, and he issued a trouble report for a fix to allow removal
of the SONAR licensed Melodyne version. I didn't get the number, but I expect it would be addressed
quickly. Contact Jörg or Ulf and tell them you want to deactivate your iLok license and go back to
computer based activation. You will then be able to open your Melodyne version reliably in editor mode.