Layers with 100% opacity, normal blend mode, no effects, and without "force own texture" enabled have effectively zero memory overhead. Changing any of those will cause the layer to render to an intermediate texture, which has a memory and performance overhead.
You should basically ignore the power-of-two size issue. The C2 engine handles it internally by assembling all images on to spritesheets which are themselves a power-of-two size. In fact the optimal size for a sprite is two pixels less than a power of two (e.g. 126x126, 62x62 etc) due to padding on the spritesheet, and the worst size is an exactly power of two size since it will pack least efficiently! So at least for sprites, just ignore powers of two and use whatever size is convenient.