I'm going to ignore convertor loss and other factors to keep this simple and get the point across. Also, this is regarding variable wattage devices.
First you have to understand what determines the amp load placed on the battery/batteries in a variable power device. Build resistance has nothing to do with it. In order to get 50w (or whatever watts, 50 is just an example) out of the chip, you have to supply it with 50w. To find the battery amp load you divide 50w by the battery voltage that is being supplied to the chip. The higher the amp load per cell, the faster the battery drains. I'm going to use 4v for single and parallel battery setups and 8v for series setups.
Single 18650
50w / 4v = 12.5a (one cell takes entire load)
Two 18650's in parallel
50w / 4v = 12.5a (6.25a per cell)(amp load is split between cells so runtime doubles compared to a single 18650)
Two 18650's in series
50w / 8v = 6.25a (6.25a per cell)(entire amp load is felt by both cells, but since the amp load is half of the 4v amp load, runtime doubles compared to a single 18650)