A HUGE part of airplane design is deciding when you've "optimised" enough. The quotes are very intentional ... no design is fully optimisied, well not with out a whole bunch of qualifying statements. In order to keep the design space small enough to come to grips with I think you need to say these parameters are primary and won't change (AUW, number of engines, number of pax, cost, schedule). Cost and schedule will obviously change (as time goes by) but the sense is not it increase the price to trade off some weight (which would also gain you range) ... neither of which are "primary parameters" (on my list, not to say your project).
But design decisions taken at conceptual design phase will only be proven far in the future ... but they can be proven wrong quite quickly, and a brave design team will acknowledge this and change direction (even at the cost of schedule) rather than keeping on pushing forward.
One example of a bad design decision is the DC-10 vs the L-1011. The DC-10 beat the L-1011 to market and established itself, and the L-1011 quickly became a market loser.
Another example of a bad design decision is (IMHO) the 737 Max. The basic airframe was pushed too far, a much earlier design than the A320 it had much lower ground clearance. This exposed it to the higher by-pass engines (bigger nacelles). The '90s redesign pushed the nacelles to have flattened bottoms. Boeing had to do something to counter the A320 Neo (the design that killed Bombardier's C-series, but that's another story). You can see the trouble they had in that it took them a year to solidify the 737 Max. Whatever happened behind closed doors, they took a bunch of decisions, and the rest is history (no belittling the hundreds of people killed).
FWIW, I think a type design should be limited to 40 years production, at which time it must be recertified. That would stop the continual "grand-fathering". Over that 40 years the design would be "brushed up", as the '37 was done, but in my world Boeing would have "clean-sheeted" the '37 in the '00s (when they were "effing" around with a variety of other designs).
"Hoffen wir mal, dass alles gut geht !"
General Paulus, Nov 1942, outside Stalingrad after the launch of Operation Uranus.