The Spanish. It's been studied in tremendous depth since the 1500s and yet it is still rich enough for elite grandmasters to surprise one another in the first ten moves.
The QGD Botvinnik is also extremely heavily studied and there are many positions that cannot be played without previously studying them.
The Sicilian Najdorf is another that requires a great deal of "book" knowledge to play well.
But in every line, there is also room to investigate new ideas.
What would you say are the most theoretical openings?
I define theoretical as having to memorize particular lines, especially forced lines, to avoid an unfavorable result.