What's a good workflow for deciding a bunch of voltages & parameters at once? Say I've got like 5 voltage ranges and 5 transistor sizes to decide on. Write a script to update the netlist, run ngspice, and re-annotate xschem? Some ngspice REPL wizardry?

There are many solutions. One is to use .param lines for all parameters (and use params instead of numbers in the schematic).

.param Wmos1=2

.param Lmos1=0.15

...

Then you can run ngspice directly on the .spice file

ngspice -i circuit.spice

You can get simulation data accessible from ngspice control language by using the

meas

command.

alterparam

+

reset

commands can be issued to run another simulation with changed parameters, so you can build an optimization loops.