I narrowed down the problem by myself by now.

Somehow it was some kind of weird interaction of an extension with the updated flash plugin. Weird because click to play seemed to work with all sites but one (and especially one with lots of embedded flash videos) after the flash update.

The extension that seemed to cause it was "Site-specific Preferences". From one day to the other (exactly the day that NPAPI plugin stopped working) the Operas click to play setting for all pages was overridden by the site specific extension settings from "Ask" to "Allow". Setting back the status within the extension to "Ask" for this specific site solved the problem.