Alright, I had a few prototype PCBs made and the result is not as dramatic regarding the CP2102 as I had feared. With just some 10 Ohm resistors placed in the UART lines and the CP2102 configured for bus-powered operation, I don't see much current drawn by the CP2102 when it's powered down. The voltage drop across any of the resistors is sub 100µV, so, practically nothing.
However, there is of course the case that the ESP32 is powered down while the CP2102 is up because the device is charging from USB. Then, the CP2102 is back-powering the ESP32 through the UART lines - not recommended, either.
So, I want to put some isolation in between and I found a 74VHCT126AFT that seems to be good for the purpose. But I'm unsure how to connect it. I could power it either from the main 3.3V power rail that is driven by the BQ25015, or from the 3.3V regulator of the CP2102. Also, where to connect the enable signal of the buffers?
It seems that the buffers are safe to be driven when the chip is not powered. So, I could power the chip from the CP2102 internal regulator. It would be powered down when USB is not connected. The buffer enable could then come from the main 3.3V rail, so the buffers would be enabled only when both power rails are present, i.e. ESP32 and CP2102 both powered.
Or, I could wire it the other way around, powering the buffers from the main 3.3V rail and connecting the enable pins to the CP2102 regulator output.
If anyone has an idea about that, I'd appreciate the input.