This just depends on the controllers you want to use. If you get two different brands then it should work fine. If they're both usb or one usb and the other uses the game port there shouldn't be issues either. The biggest issue is that some controllers drivers don't support more than one of the same controller on one pc.
I highly recommend the SmartJoy PLUS adapter that allows you to use PSX and PS2 controllers with your pc, since it doesn't require drivers except for the rumble functions, and all functions work except for pressure sensitive buttons, but there isn't any computer software that would support them anyway. This system does support multiple controllers. To make things easier and less expensive you could by the dual version that has two controller plugs right on it.