S2 enables / disables the reset line. The reset line (available also on 2 contacts of the B2B connector) resets the USB microcontroller and the FPGA.
S2 has to be turned off (Reset) if the user wants to program the SPI Flash memory in direct mode. For programming the SPI Flash memory in indirect mode over JTAG, S2 has to be turned on (Run).

S2

label

position

ON*

RunĀ 

system running

OFF

ResetĀ 

system reset


For further information, please read this configuration paragraph and this other.