The days of a dodgy chieftain running on shoestrings are over, the regs and safety just won't allow it.
Maybe the regs "just won't allow it", but where do you get the safety part from?
Air North for example ran for a number of years using Aero Commander 680FL' by 2, an Aero Commander 500, and eventually Herons.
It was all SPIFR, apart from the Herons, which had no auto pilot, a typical days run was RO-AA-KO-AA-GS-RO-AA-RO, one was also the ticket seller at the outstations, baggage loader, and any other task that was required. All this with a staff of no more than 4 full time pilots, and a couple of part timers required for right hand seat in the Herons.
It must have been a safe operation as I do not recall any accidents, and certainly no injuries to any Pax.
If it could be done then, I see no reason why someone could not step in to fill the gaps. From memory Bellair ran for some years with just an WK-AA-WK run, again SPIFR with an Aztec.