Upon reviewing this concept, I still think it is important to introduce more design challenges for the player to contend with. Based on discussions above, I ultimately think three things would sufficiently present a good level of detail for the player to consider the holistic composition of their organism:
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Implement a non-linear osmoregulation cost that scales with size. This will represent the challenges volume presents to the player and provide a way to counter huge size.
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Count the number of exposed surfaces. Or this could just be the number of hexes on the outside of the cell if that works better. We would just need a number to base effects on environmental tolerances, toxin resistance, and (if agreed upon) health.
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Implement the surface-adjacency bonuses proposed by Buckly to locally represent the benefits of surface exposure. This will make balancing easier and introduces another level of decision making so players are thinking a bit more than “what part do I need”.
1 is already discussed in the context of general balancing, so 2 and 3 are really the proposals unique to this thread. I do think they are worthwhile additions.