The FETs driven by an PV optcouplers should be relatively insensitive to RF interference as they are either all the way off or all the way on.
The PV optocouplers provide a floating supply to drive the fets. This is essentially the circuit inside of Photomos relays, just with the parts separated, so that the heat from the LEDs can be a little separate from the signal path and possible thermal EMF effects.
The relay K502 schould not be that critical - it is even optional. The MOSFET stage for the protection can also be used as a switch. K502 would be more to reduce the leakage. Even when off the FETs 503/504 can still have a resistance in the GOhm range.
For the relay K501 one can use 2 contacts in series if needed. This is not so much for the path from the input to the divider, but from the divider to the ACAL signals.
For the first test / proof of pronciple I would consider limiting the voltage a little to get away with simpler / smaller relays. MOSFETs for more than 1000 V also get expensive and sometimes tricky to get.
To keep fast spikes from ESD away from the MOSFET there should be some series inductance (e.g. 100 µH, maybe more) and ideally also some capacitance to ground already before the FETs.
THT resistors for R501 and maybe R502 can make sense - they don't have to be metal film or low noise. The point is only low thermal EMF. With respect to thermal EMF effects resistos vary a lot and not much data are found, except for good shunt resistors.
Having both a positive and negative signal for ACAL is not much extra effort - the much for the low voltage signals can be a HC4051 or simular. It can help with averaging over 2 points and this way get less effect of the ADCs INL and it gives an extra check in the self test. So I would consider it worth the little extra effort.
Chances are one would need more input paths in MUX. I would consider a 4051 for low voltage signals (+-1 V, +-100 mV, Temperature sensor, optional shunts for current ranges). Another MUX (e.g. DG408 or ADG1208) could be used for less critical signals like the ACAL signal for the divider, buffered signals (e.g. ohm sense L, low current TIA). The sepration to a 2nd / 3 rd mux also has the advantage to allow better isolation from open, unused inputs that would pick up hum. Depending on how current ranges are implemented there may not be many spare input left.
For the gain setting resistors I would not really consider the Caddock HV arrays. They are quite expensive and may be noisy as they are thick film.
The VTF330 looks good and noise wise should very likely be good or at least good enough. If really needed to get a lower resistance one could have 2 such arrays in parallel as an option.
The total resistance is a compromose between nonlinearity from self heating and noise. This would mainly effect the 1 V range, though not that much: In the current plan R501 and R502 already give 10 K of resistance that contributes to the noise.
There is one more option for the gain setting resistors: one could use a larger number of equal resistors. With 10 in series, 1 and 9 in parallel one get a 100:10:1 ratio. 20 equal thin film resistors are not too bad, though the matching is usually not specified, but usually good. The TC specs for the resistors are usually for a quite large range and the performance is the more relevant 20-40 C range is usually quite a lot better. This also applies to the VTF330.
Chances are the 4053 should have about matching capacitors on both the input and output side. One could use somewhat different values to trim / shift the charge injection a little. So there should definitely be footprints, even if one may not be used later. I doubt that R518 would be of any use. If at all a resistor for the C1 input may be useful.
To keep the currents to C503 and the charge injetion at the 4053 local to the floating level, I would prefer to not have an extra OP-amp for the bootstrapped supply. So U501 would directly drive the ground side of the 4053. To reduce the AC current from the control signal on could use a series RC from the 4053 GND to the raw control signal (TP501). R506 should be the same as R509 - probably more 100 K may be 47 K. This way U501 should not see relevant fast current spikes and the charge spikes should stay mainly local.
For the ground the distinction in power ground, signal ground without current and signal ground with current makes sense. Even than one should compensate the ground current if possibly (e.g. for the current from the gain setting resistors).
For the main amplifier the OPA140 may not be good enough with the linearity. I have not tested the OPA140, but for the slower brother OPA145 I have seen around 1-2 µV of output cross over error when used as a buffer. When used with gain this error would be way to high. One could reduce this output cross over error in a compound amplifier with a 2nd OP to drive the ouput, though this is a bit tricky with the rather fast OPA140. The other point is the limited CMRR: the specs are only 140 dB typical / 126 dB min and would not guarantee better than 0.1 ppm INL. It may still be Ok as the linear part of the CMRR would not cause an INL error, but just a marginal change in the gain. The problem is that we can't be shure that the OPA140 is linear enough.
When used with a CMOS MUX to switch the gain, the parasitic capacitance to ground can cause stability problems. So one would likely need extra capacitors at the gain setting resistors to compensate.
I have looked at the amplifier circuit used in the 3458. The advantage there is that bootstrapping the input JFETs is relatively easy (compared to a bootstrapped OP-amp). The extra input stage adds overall DC gain and allows to compensate for more if the linearity errors like the output stage cross over. The part with the inductors at the JFETs is unusual, but it makes sense, at least for a gain of 1 and just boarderline for a gain of 10. It reduces the gain for the highest frequency and this way helps with stabilty (need need for 100 MHz range GBW). However I still don't understand stability with a gain of 100 here the simple analysis show a tendency to oscillation. Maybe the capacitane of the JFETs used for gain switching save the day.