Is there a practical difference to connecting batteries in series or parallel when routed through switched/regulated output?
Consider two batteries, that can be connected in either series, or parallel. 

Each battery has the same voltage, and if we assume each delivers the same power, has the same current being drawn from it. The total output power for either connection will be the same.

Each will have the same power lost to internal resistance, as the current in each battery is the same, so the efficiency will be the same.

Given that they are driving an ideal SMPS, it doesn't matter whether it is fed its 2VI power as 2VxI (series), or Vx2I (parallel), the SMPS output power will be the same.

There is no difference between series and parallel connection for power or efficiency. There may be some practical differences however.

The wiring between the batteries and the SMPS can be lighter in the series case, as it carries half the current.

Series connection often results in simpler wiring and less of it.

The SMPS you have might be able to work up to V, but not 2V, so you couldn't use the series connection without buying new stuff. If it's able to work at both voltages, it might have different efficiency at them.

Parallel batteries need to be balanced in voltage before being connected, but once connected can be charged/discharged as one, they can even be different capacities, as long as they are the same chemistry and voltage. Series batteries need to be balanced in charge state at all times. This is easy to maintain with lead and nickel batteries, as they can accept overcharge to balance their charge state. Lithium needs active charge state balance, as they cannot be safely overcharged. In practice this is not a limitation, as chargers that balance, and BMS ICs are now readily available.