If you're running in a single-tasking environment such as DOS, it's best to turn async off, as SC will have realtime control over the parallel port and thus should be able to handle a faster synchronous transfer. However, if you ever want to use SC from within the Win9x GUI (I did this occasionally for C64 development), you'll have to turn async on. If you plan to use SC in both DOS mode and the GUI, I found it best to make two copies of the config file, one with async on, one with it off. Then, I merely set up two batch files - one for async and one for synchronous. Each batch file echo'd a bit of information regarding the circumstances that are best for each setting, then copied the respective config file to the name SC expected, then launched SC.
However, if you can't get SC to work at all with async off, it's worth trying it with async on. It'll probably only really work in Normal mode, but an async normal mode is better than none at all.