I do think the secret here is not the maximum fuel capacity (as in the first design), but the processing speed. When it comes time to improve the ships (engines most likely), I'm considering reducing the capacity to 25 fuel systems and putting in more processors.
With a faster ship, that would be more cost effective as you are making more round trips.
While I think you are right about increasing the number of harvester modules and decreasing the fuel capacity, I'm not sure speed is so important. I think you are much more likely to need to return for refit before you fill up the fuel tanks, unless you really, really, skimp on the tankage.
Kurt
The second design I have above, 50 replacement parts, fuel capacity of 2.5 million liters. If I modify the design to 1.25million liters, and double production, it would take just under 10.5 years to fill. That is not counting any technical increase in production rates via research. By previous experience, a ship like this can last around 8-9 years before requiring an overhaul (under 5 replacement parts). An increase from 12 to 14 in production rates would drop the "full up" time to just under 9 years.
To me, when it gets to the point where the full-up time is less than a required overhaul time, then I want it to get to the depot to release its cargo as fast as it can, and get back on station.