There's pros and cons to having multiple files, but I keep all of mine in the same ISBoxer profile. The only time I would recommend having multiple files is if it simplifies something that you wouldn't otherwise understand how to do, or it would just be too much work.

For example, if you have multiple PCs, the automatic FTL built into ISBoxer won't currently work across both PCs. You can work around it by specifying the FTL macros. If you're using the Quick Setup Wizard, it's easiest to just modify it in the General key map. But by doing that, you break it for other Character Sets. So in this specific instance, it would be easier configuration-wise to have multiple files for different sets, though it would be more annoying to switch between the sets at play time.

No other good reason for using multiple ISBoxer config files comes to mind; in general keeping them all together is best. The feature is there to facilitate whatever you'd like to do though, so in the end it's down to personal preference.