La Liga champions Atleti have the chance to go second in the table by beating Barca at Camp Nou on Sunday.
Atleti then travel to the Santiago Bernabeu on Thursday to contest the second leg of their Copa del Rey tie with Real, which Simeone's men lead 2-0 from last Wednesday's first contest.
The Argentine coach is eagerly anticipating the challenge and is well aware of the contrast in style between Barca and Real.
"They are two great teams, among the best in the world," he said. "But they play differently.
"One plays more vertically, Real Madrid, although now with Isco and James [Rodriguez] in midfield they keep more of the ball, whilst being a very attacking team.
"And Barcelona, with [Ivan] Rakitic and Neymar, are a team with a lot of possession and great individuals in each part of the pitch.
"They can also play in many different ways too, and keeping what made them the best team in the world.
"Results last year weren't the best for them, because they found us on the way. But their DNA is still there. They have great pressure, great link-up, a wider game vision with Rakitic, velocity with Neymar and Jordi Alba.
"And they have [Luis] Suarez, the best number nine - a very complete team."
