The success of running a Helix into an amp, whether straight into the front, into the power amp, or in 4cm, will depend to some extent on the specific amp.
I have been using the Helix in 4cm with a Fuchs ODS for a couple of months. It took some time to dial in, but I am at this point very happy with how it all sounds and works.
I specifically got the Helix to use predominantly in that setup, with the Fuchs. I might use it into FRFR once in a while, but for me the attraction of the Helix was that it replaced a bulky, heavy, expensive pedalboard with a device that is lighter, smaller, easier to transport, less expensive, and more flexible.
So my view is that if you have a great amp, the Helix can integrate well into that type of setup.