In other words, the best option is the one where the impedance if of the
drivers and amp are matched? If so, what about using an amp that wants 4
or
16 - could there be any differences, in terms of driver control, between
them?
Simplifying things, let's say the amp output impedance is zero ohms and it
tries to maintain its voltage gain whatever the load. So whether the
speaker is 4 or 16 ohms, it has the same voltage across the terminals.
Using Ohms Law, I = V/R, using a 4 ohm load demands more current from the
amp.

If you have two drivers in parallel, the ~4 ohm load may mean the amp cannot
source enough instantaneous current producing poor bass quality. However,
the back emf from each driver is shorted by the source which damps down the
oscillations in the driver improving driver control.

If the two drivers are in series, then the amp would find it easier to
source the current and therefore maintaining voltage gain. The source
impedance for each driver is now zero ohms plus 8 ohms, which will change
the damping in the drivers ie. poorer driver control.

By good driver control, lets assume we require the instantaneous air
pressure pushed by both drivers in enclosure is proportional to the
instantaneous voltage level at the power amp input. I would therefore put
both drivers in parallel and ensure your power amp can drive a 4 ohm load
for better driver control. ie choose an amp that can source large current.


The amplifier will likely be solid state, 50-100W per channel, maybe
with a low-pass filter at the input (because that seems like a good
place to put it - all of the amp's work is going into the wanted
frequencies).

Yes, this will reduce IMD too.

Cool. That sounds like a good thing to have.
IMD is just another form of distortion caused when 2 or more frequencies go
through a non-linear system.