shrug it's honestly going to be a bit hard to compare. But for a rough guess, the AN-225 can lift like 300,000kg, and the AN-124 (from which its derived from) can lift like 230,000kg. The AN-225 has 6 of the same engines that the AN-124 has, so naively assuming roughly the same fuel use, the lift ratio is ~ 1.34 to 1 and the fuel use ratio is ~ 1.5 to 1. And the AN-124 is sufficiently cheap to operate to be in use commercially.

So by those rough guesses, the AN-225 should be ok.

That said, the moment you have a too heavy, or too big load for an AN-124, then the extra fuel cost of the AN-225 has almost infinite value.

The drawbacks to scale always have to do with complexity, and ground infrastructure. The AN-225 can't operate from as wide a variety of fields that the AN-124 can (though this shouldn't be a huge concern from commercial use).

Structurally, the modifications from the AN-124 to AN-225 aren't super complex. They basically added plugs before and after the wings to extend the fuselage, and added a wing extension. While these aren't trivial changes to an aircraft, they're basically the simplest type of structural change you can make. Oh, I guess there's a tail modification, but that's not that risky either.

I mean I guess the point is that you probaly would not want a whole-scale replacement of AN-124 class lifters with AN-225, but keeping a few around enables entire types of lifts (and therefore operations) that simply aren't possible. The key would be to estimate what the appropriate amount of AN-225 are.

For an example, the famous Beluga Airbus enables a form of manufacturing distribution (for good or for bad) that simply isn't possible without it existing. You would never want a giant fleet of Beluga, but having it is invaluable.