I've found many similar questions, and hate to ask something so similar, but my goal is to get usb power (4A continuous) from 4 18650 Li-Ion cells. I'm debating putting them in parallel and using a simple boost circuit to get them up from 2-4.2 volts to the required 5 volts, or putting them in series and using a simple car charger to bring it down. What would give me better performance/battery life, and also, be easier on the batteries?
To first order, there will be no difference in efficiency. They are both 100%, less 5% to 20% of losses, depending on how good the 'stuff' you build it from is.
Taking the same amount of power from the same number of cells results in the same performance.
The series and car charger route sounds easier to source, and will use lower currents between the battery and converter. But there are plenty of ICs designed to do the 3-4v up to 5v job! Your min voltage of 2v might be a bit optimistic, most authorities put the minimum voltage higher for reasonable cell life.
All batts in parallel would obviate the need for cell balancing on charge, and individual under-voltage monitoring on discharge. If you had them in series, you would need cell balancing, but a standard charger would include that, it's only an additional problem for home-brew solutions. Do charge them properly BTW. It may be that the charger determines which solution you pick.