You don't use Run/Stop to start a game on a C64.
On a real C64, press Shift+Run/Stop to load and start a game from tape.
In CCS64, you can drag-and-drop a disk or tape image to the CCS64 window to run the first program in that image.
Look, On the intro screen for the writer who remade Pipeline for the Emulator it shows to press run/stop to exit the instructions but I can't get it to do anything past that screen.
If a program asks you to press run/stop, you have to press the Esc key in CCS64.
Also, if the game makes use of a joystick, you have to configure that in menu Alt/I (choose a keyset i, choose a keyset for Control Port 1 OR Control Port 2).