a simple 8 bit shift register can drive two nixies.
so one 'module' would be one 8 bit shift register, two 74142 and an array of HV drivers. it would be a nice compartimentalized module ready for cloning. you could even use an i2c io expander instead of a shift register.
drive two nixies directly from an i2c bus.
The way I'd have done it :
Route one nixie to a line of 10 pads, whichever way is easiest for layout. Repeat for each digit.
Route one driver to a line of pads, whichever way is easiest for layout. Repeat for each driver, spaced at 8/10ths of the nixie spacing.
Route the pad rows together in order, then delete the pads.
Easy to route, and easy to re-use if you remember to save a copy of the nixie+pads and driver+pads.
The mapping from drivers to nixies is consistent so you only need to do mapping for one digit. You can treat the whole display as a string of bits, ten per tube, all shifted out to the drivers.
If there are any unused outputs, have them at the far end so you don't need to worry about padding.
If your hardware supports 10 bit SPI, even simpler, If not, bit-bash it as speed isn't going to be an issue, and probably simpler than merging the 10-bit values together to form whatever word size your SPI port likes, but you could easily do the latter if you wanted.