Rechargeable battery configuration for 5V
In general, resistance is the main reason for power loss, where the power lost is proportional to the current squared for a given resistance. This includes the internal resistance of the cells themselves, as well as the resistance in your wiring and your power conversion circuit elements.

So, in general, when you have a choice, select a configuration that uses higher voltages and lower currents wherever possible. This would mean putting the cells in series and using a switchmode buck regulator to power your load.