I tested it the last two days. The remainder of the flight, the return flight and again the same two flights yesterday no problem occurred. So almost two days and four long hauls without any issue.
Today it crashed again, almost at the same position as mostly. I started P3D again, continued the flight and when after 10 minutes nothing happened, I reloaded the scenario (which was saved around 4 minutes before it crashed). The scenario loading worked and the message "Regenerating airport cache" appeared. Then couatl.exe crashed with a message and P3D crashed (to desktop) without any error. Windows error log shows a crash in api.dll. I tried it again and first the scenario worked without any problem. Then I loaded it again when after 15 minutes no crash occurred and again the same happened. Loading worked, the aircraft started flying. "Regenerating airport cache" appeared, couatl.exe crashed and P3D crashed to desktop.
That and also the fact that it always crashed close to the coast (mostly around Scotland, once around Greenland and a few times 90 NM off the coast of Newfoundland) makes me thinking if there might be a problem with the airport cache or at least something linked to that?