Now that everyone is using finfet processes, the layout part is pretty easy to solve because transistor widths have to be a certain number of fins and the layout is extremely regular.
One thing your analysis didn't include, which actually ends up being quite significant, is the extra capacitance caused by the wires between transistors. This changes the sizing requirements substantially.
I've done some custom logic cell design, and I always had to use a lot of trial and error, though generally I was concerned more with speed than area. I'm not sure exactly what the development process is at my current employer, but it seems like its a lot of manual work. I'm guessing they set area targets based on experience and attempt to maximize speed where possible.
Ultimately, everything gets placed and routed by a computer anyways!