We will have to disagree.
Okay, let me explain why I said what I said, and you are free to disagree if you wish.
Rate of closure of two vehicles traveling in opposite directions toward each other at 60 MPH is roughly 176 ft./second.
At 100 yards, if the gunman fires, and not allowing for the fraction of a second for the bullet to impact the target vehicle, the target has less than two (1.7) seconds to realize they are under attack, identify the threat, and mount a defense.
By that time, the shooter's vehicle has passed.
Even at 30 MPH (both vehicles) with the time to identify and react expanded to 3.4 seconds, not many people would be able to:
1: realize they are under attack.
2: identify the source of the threat.
3: produce their weapon, target the threat, and fire. ---especially while driving.
With windows up and radio on, few would even hear the shot, and likely would first realize something was wrong when their glass broke or a bullet impacted their vehicle. By then, the attacker's vehicle has passed.
Deploying a rifle would take even longer.
Stopping and getting out to fire (at 60 MPH) would take close to 5 seconds, if you are fast, by which time the shooter is motoring along at 88 feet per second, so add your stopping distance (~130 ft. to stop), plus the 440 ft. the shooter has traveled since they passed you and you have to pull a 200 yard+ snap shot on a target moving away. Even with a rifle, that can be a difficult shot.
This isn't Iraq, people here aren't on full alert, especially just driving down the highway. For all practical purposes, they will not be able to mount an armed response to the shooter under the circumstances described.
If you halve the speed (to 30 MPH), you cut reaction and stopping distance and increase time of closure, which makes it slightly more possible, but a handgun shot at a vehicle is tough enough, and if your window is up, you have to shoot through the glass or lose the opportunity to shoot at all. From 100 yards, you have 3.4 seconds to recognize you are under attack, identify the threat, produce your weapon and fire, only enhanced time wise by hitting the brake and keeping yourself in the line of fire as well. After that, the shooter is past you (and you are technically on the offensive). If they are still shooting, you should be legally covered by clauses in most lethal force laws allowing for intervention on behalf of third parties, but you have a diminishing target, and a short sight radius. If you are good you can expect to get off 3-7 shots with a semiauto handgun, at the shooter's back. That assumes the shooter is alone, with no one in the back seat (kid in a car carrier, etc.).
Stopping distance information taken from
https://nacto.org/docs/usdg/vehicle_stopping_distance_and_time_upenn.pdfPlease note the braking times given are not including reaction time.
About the only defense you can mount is to hit the shooter head on, and hope your air bags save you.