If you’re using an external FTDI or CP2102 interface board to program your Mayfly via the Mayfly’s FTDI socket, then the Mayfly dipswitch labeled USB should be turned off before connecting the external interface to the Mayfly, and it should stay off the entire time.
What version of the Arduino IDE are you using? From your screenshot, it looks like you might be using one of the newer versions. On our software instructions page here: https://www.envirodiy.org/mayfly/software/ we recommend that you use the Legacy v1.8.x version since there are some quirks about the newer v2.0 and web-based Arduino IDE’s that can cause issues with the Mayfly.
When you plug your CP2102 Friend into your computer’s USB port, what does Windows Device Manager say? Does a “Silicon Labs CP210x USB to UART Bridge (COMx)” show up under the “Ports (COM & LPT)” list, or is it shown under an Unknown Device tab with a yellow triangle?