Pi Pico W datasheet states:
3V3_EN connects to the on-board SMPS enable pin, and is pulled high (to VSYS) via a 100kΩ resistor. To disable the 3.3V (which also de-powers the RP2040), short this pin low.
RUN is the RP2040 enable pin, and has an internal (on-chip) pull-up resistor to 3.3V of about ~50kΩ. To reset RP2040, short this pin low.
Which means that RUN resets the microcontroller and 3V3_EN powers it off. Practically (in application) both sound to me as they will only reset the microcontroller. I tried also using both pins and haven't noticed any difference in the behavior: microcontroller starts over, once the pin is released (i.e. pulled up again).
So, the question is, what is the practical difference between using RUN pin or 3V3_EN in applications?