While Andy's suggestion may or may not did the complete trick, reducing the screen resolution also helped. So, when selecting either the Mk.II or Mk.V in the UI, their Initializer comes online but as soon as I hit 'Fly', the process is cancelled and the selected aircraft flies in 'stock mode' (not RSM). When I end the flight, their respective CleanUp.exe processes run. Back in the UI, the Initializer is active again but when I hit 'Fly' a second time, CFS3 usually crashes.

EDIT: I played some more and sometimes there is a process called 'ClickDisabled.exe' that seems to prevent any mouseclick in the UI, even in programs outside of the CFS3 window...