Hey again,
it took some time but I was able to resolve my issues. It seems that it was indeed an issue with the power supply of the external 2.5 drive, even when using an active USB hub. I then replaced the drive with an external 3.5 drive and didn't have any issues so far, even with high load. There is also a performance gain with the other drive, so I will not try to make the smaller drive work with the rpi any longer.
Thank you for your help!
RPI 4 won't boot with usb hub Topic is solved
Re: RPI 4 won't boot with usb hub
good you found it and it's working now 
Pls let us know if a solution is working. This could help others if they hit by similar situation. Your DietPi Team