I've been getting great results using my Helix as a processor/switcher for several instruments in a live rig (electric guitars, acoustic guitar, pedal steel and an electric mandolin).
My two electric guitars fire into the standard guitar input via a Radial Big Shot I/O and each of the other instruments mentioned use a unique separate FX return for each (Acoustic Guitar=Return 1, Pedal Steel=Return 2, Mandolin = Return=3). In a preset I place a return block at the front of my signal path and routed for that particular return/instrument, and then I've got the ability to quickly and simply change instruments live by selecting different presets.
Awesome flexibility and to date, this has been my best solution to integrate all of the above instruments. The one shortcoming that I'm trying to resolve is I can't access the tuner function on any of these particular "return ins" without manually having to switch the tuner to receive on that specific return channel. Unfortunately the tuner receive settings appears to be global to all presets and does not include the return channels in the basic tuner setting called "Multi" which includes Guitar, Aux & Variax only. As it stands, I can only have tuner function for my electrics connected to the guitar input jack.
I really want to be able to use the internal tuner for all of these instruments whenever I switch to their presets... Maybe I'm missing something? If not, perhaps Line 6 might address this in a future update. Although I would imagine this would be a fairly low priority since I doubt that many users are attempting using the Helix with multiple instruments like this.