My dad has a 2007 Lexus RX350 (no longer the RX330). He drives a lot on the highway and already has 51,xxx kilometers on the car. It's great...no problems whatsoever. He really wanted to get something reliable so we went with the Lexus. If reliability is your priority, I'd stick with either the Lexus or Acura.
I was trying to get him to get either the Volvo XC90 or Landrover LR3...but both have their share of reliability problems.