You might prefer to use the Reference plugin in cases where low latency is important or if your setup requires a more complex audio routing solution than Systemwide currently supports.
Adding Systemwide in the chain between your DAW and audio interface results in increased latency (around 20-60ms). This can become an issue when recording audio or MIDI so it's best to use the plugin in such cases.
Systemwide on the other hand has a serious advantage - you won't need to worry about bypassing the plug-in for rendering your mix. If your configuration requires using the Reference plugin, remember - you can still use Systemwide in parallel for all other audio on your system.
Systemwide currently still doesn't support ASIO, but we are working on that already. Our goal is to eventually reach a point where Systemwide can be the primary module of the software featuring all the necessary routing, latency and automation capability among other new features.