Yes, you can have up to four independent, parallel stereo paths. Any input or FX return can be the the input for a path. I currently have mine configured this way:
Path 1: JTV-69 Magnetic pickups (via VDI cable) -> EHX LesterG rotary pedal (via FX send/return 1&2)
Path 2: JTV-69 Variax models (via VDI cable)
Path 3: EHX Key9 pedal set to Suitcase Rhodes (via FX send 3, return to aux input)
Path 4: GR-55 guitar synth (vix FX return 3&4) (note I have FX send 4 feeding an EXH B9 pedal HACKED input into the guitar INPUT of the GR-55)
(I also have the Helix AMP control out patched into a HACKED input for remote toggling of the GR-55's CTL pedal.)
Thus I have four different signal paths going at once, each with their own Helix FX.
The Helix is VERY powerful.