Learn French: Prends le train plutôt que la voiture. - Take the train rather than the car.

Yes! You could absolutely say Prends le train au lieu de la voiture (Take the train instead of the car). While au lieu de focuses strictly on replacing one thing with another, and plutôt que emphasizes a preference ("rather than"), they are practically interchangeable in a sentence like this.

Why is it plutôt que and not plutôt de?

The expression for "rather than" is always plutôt que. Because it means almost the same thing as au lieu de (instead of), learners often mix up the prepositions. Just remember the pairs are fixed: plutôt always goes with que, and au lieu always goes with de.

Why does Prends have an s at the end? I thought we drop the s for tu commands?

You only drop the s in the tu command form for verbs that end in -er (like Regarde ! or Mange !). Because prendre is an -re verb, its tu command form keeps the s: Prends !

Do I really need the la before voiture?