I feel like the problem is the a321f cant replace the 757f well enough. Range is just a bit short, and payload eff is lower since its per ton fuel eff is not much better and its still uses 2 crew member, and charges routes fees and such. From many bases, you will need to serve hundreds of level 2 airports which will never really go to lvl 3, in the US alone there is usually multiple pages of cargo you need to serve with lvl 2. If you are based anywhere outside the US you will need 757f to reach this cargo, double stopping really has much lower margins that single stop, and the sheer number of a321f you would need to fly all the lvl2 airport cargo is somewhat unfeasible, say in the current LHR Im doing in gw1, I already have 300 757 sized freighters in London f in london flying exclusively cargo to lvl 2 airports, and the demand will more than double in the next 15 years, if this gameworld remotely follows gw2 in cargo demand.
There will be even more airports which upgrade to lvl 2 and need a flight. Anyways, I just dont think there is a realistic substitute for 757f, and cargo is too important to ignore all the lvl 2 cargo. The lvl 2 airport cargo market is LHR for example, is worth about 350-400million a week in the 1990's. sure, some airports will upgrade to lvl 3, but also lvl 1 airports will ug to lvl 2 opening new markets for 757 cargo. Also, I dont think it matters that its pax variant is useless by game ends, since the a330, and a320 covers so much of the market on its own. The only thing it lacks, is a good 8000nm+ range option, since the a340 is quite depricated by a games end, but I think that too is underated in most worlds since the a340 has killer belly cargo, can can make up for its inefficiencies there flying more belly cargo than say a dreamliner. just a few thousand kg of belly cargo will make up the inefficiency. a320 is nearly a perfect large fleet type, best small cargo plane, I think the 321NEO is a perfect pax plane, a330-900neo is also not much worse than a350/777x/787, especially the 777. I dont understand why so many people go 777 when they are almost never full anyway unless you have no competitor.