I'd think directed energy weapons (e.g.: lasers) would probably be effective here.

Any Mach-20 vehicle is going to have an extremely limited thermal tolerance, and thermal shielding is likely to be applied specifically to those elements of the vehicle which require it for aerodynamic reasons.

Lasers could acquire and track with the target despite evasive maneuvers better than any kinetic weapon. Though a large-dispersion scatter weapon (ball bearings) would probably be sufficient. Each bb impact would be about the equivalent of a gram or two of TNT.

We already have the technology to shoot it down and have done for years:

http://www.raytheon.com/capabilities/products/ekv/

Inevitably, someone else probably has it too.

The US Air Force understands the concept of high speed spy planes with the SR-71 and knows how to deal with intercept attempts. A slight turn takes the plane well away from harm.

[edit] now if the enemy builds its own with the same speed / range then all bets are off

When you're flying in a straight line, which at these speeds this plane, unlike the SR-71, will be doing, it is only a matter of time until another Zoltan Dani comes along and pops it out of the sky.

You and all the down voters are crazy if you don't believe this thing can change directions. Looking at the whole D-21 / SR-71 program for what this do.

Do the math. It will have a turning radius measured in the hundreds of miles.

that is still a turn and given the need to line up a shot, just as effective.

It's a turn wide enough to be effectively a straight line over a good deal of countries. We don't have to calculate out trajectories on the backs of notebooks anymore, we have systems that can do that in milliseconds.

This is just one more in a long line of "unshootable"/"unsinkable" projects which will prove the opposite.