One thing that I recently thought of when it comes to the implementation of a size/cell count cost in the form of an ATP cost (as opposed to some other reduction in effectiveness):
Even if you compensate for it through specialization and adjacency effects, it’s still going to require you to consume more glucose or other external resources in order to survive. There’s no real way to offset that through species design. If you’re photosynthesizing, that makes no difference, but for most other energy sources it’s a big penalty, especially for predators.