in terms of personal decision making, I've always focused on how much does it cost me to travel one pax on 1 nm with each plane; i've got a pretty big Excel sheet doing this (actually, I've been using and improving it for about 4 or 5 game worlds.;; so it's starting to be pretty big now lol).
Basically the idea behind that is that you should decide for yourself which parameters you want to take into account, then compare your aircrafts according to those parameters and choose what the best option is according to your expected use. To me, it's cost per pax per nm, to which I add leasing cost, maintenance costs, est. landing fees,... all reported over 1 day.
Then, I can decide "ok, i want to do a CDG-NRT route... i've got a bunch of 3 good planes to use, which one is better". i enter their data and ACTUAL LEASING COSTS, then choose the best one.
In my experience, LH is where I clearly do my money, since I standardize and cut costs a lot. Moreover, I always consider each route as independant, so that i make them all breaking even. b767 is not a good profit maker as for my strartegy, but it might be according to your priorities. I believe B773, A332 and A346X are great.
But as usual, this is only a guideline. I'm not crazy enough to decide to do CDG-JFK with A332 simply because it looks more fuel efficient. There's a lot of competition on this route and few slots available, so I'd better take B747 or A380 to maximize the route. Indeed, competition through frequency is not a good choice there.
Up to you
BTW, it must sound obvious, but I strongly recommend to sign only for 1-y long leases. it becomes cheaper when renewed after one year :=)
Hope this helps.
Have a great game