On an expendable rocket, every bit of inefficiency is more engine, tank, and structure that you have to rebuild for each launch. You want to minimize that. It's also extra fuel, but relative to the total cost of a launch, fuel is essentially free.

If you can reuse the rocket, then that becomes much less important. Maybe you spend 10-100x more building engines and tanks and structures than you would if you had a more efficient design, but you get to amortize that cost across many launches, so it's much less important.

Reuse is, of course, a big if. A gigantic if. The gigantic-est of all ifs. The big question is, "will it work?" If the technology simply doesn't work, or if it "works" to get to orbit but requires so much refurbishment that it's basically like building a whole new rocket each time (see: Space Shuttle), then it's not practical. But if it does work, then who cares if you drag 10x more mass to orbit than you strictly need to?

I am very much in a "I'll believe it when I see it" mode with Skylon, but to me the objections center around the the hard work of going from theory to practice, and the lack of visible progress with same.