You CAN, but in general the cases are built to be closed. I had the side off my case last night and the temps on my cpu and video card came down about 5-10 degrees when i put the side of the case back on. In general if you have a good intake and exhaust fan keeping the case closed is going to direct the airflow over the components and out correctly, whereas if you have the side off there is no real air flow and you will get a lot of standing air.