The main advantage Skylon would have over the Falcon 9 is the fact that the Falcon 9 is not fully reusable because they don't and can't recover the second stage, while the entire Skylon is recovered.
That's significant, of course. The second stage makes up about 25% the cost of the rocket, so that places a ceiling of about 75% on how much Falcon 9 reusability can save..
But then, starting from where the Falcon 9 is now, building a new rocket that can also recover the second stage doesn't seem too difficult. It's a big challenge, to be sure, but relative to Skylon it's not too bad.
Skylon is certainly much more ambitious in terms of how it works, but it doesn't seem to be very ambitious in terms of what it can do, which is not a promising combination.