there have been issues with USB to serial cables..
actually MegaSquirt states it directly in their website
You need Windows 95/98/ME/XP and a conventional serial port to communicate with MegaSquirt. USB will NOT work directly, however some people have reported that they have been successful using a USB-serial adapter. You do not need a fast computer to tune MegaSquirt, just about any computer that is capable of booting Windows 95 (or better) will be fast enough, but get the fastest machine you think is reasonably priced.