“Prendre la route” seems better here. “Reprendre la route” suppose it stopped, then started moving again.

However, none of those expressions are great fit here, it is used usually to describe someone‘s state, like being on a road trip. I would not use it for other things than people.

I would say “s’il prend la direction de la Terre” in your case.

I think route in French is less used in the sense of course than it is in English. That’s the main problem with your sentence. I’d use cap and say :

• Je ne suis peut-être pas expert en astronomie, mais… Qu’est-ce qu’un petit humain de rien du tout peut contre quelque chose d’aussi imposant, s’il change de cap et fonce sur la Terre ?

Je ne suis peut-être pas un expert en astronomie, mais, que peut faire un humain insignifiant face à un astéroïde aussi imposant si celui-ci poursuit sa trajectoire en direction de la Terre ?

Can you say “prendre la route” here instead of “reprendre la route”?

Grammatically, you can remove a piece of information by using prendre instead of reprendre, but scientifically, I would have avoided to use reprendre in the first place.

Asteroids, like planets, stars, galaxies, black holes and the likes do not change their direction on their own.

Prendre la route, reprendre la route, prendre la direction or, to a lesser extent, changer de cap would mean there is a pilot on board to make that decision.

All of these bodies cannot defy the fundamentals of gravitation. They just follow its laws.

A collision between two objects in space is expected to trigger a change in their respective trajectories, especially the lighter of them. In that case prendre la route would make sense as there is some kind of “driving decision” during the collision.

I would nevertheless suggest:

Que peut faire un misérable terrien contre quelque chose d’aussi phénoménal si sa trajectoire vient à croiser celle de la Terre ?

For me prend sound better.

reprend la route direction Terre imply to me it was in the past in a route to earth, felt on another route and now return to the route to the Earth. A bit like if I told it retake the road to Earth.

To use reprend I would had told;

reprend sa route mais direction terre.

The use of trajectoire or cap like @jlliagre and @petitrien told sound more good and specific, but I wanted to add the detail of reprendre use.