We bought our RX450h new and have driven it daily since. It is not a car for the performance oriented driver. It is a room, comfortable cruiser that gets impressive gasoline mileage in town. On the highway it is smooth and quiet. The hybrid drive has worked great, and we've had no problems with the system. After 70K miles, I can report only one significant mechanical problem, which could very well have been catastrophic. An oil hose burst and the car leaked oil all over our garage a driveway. Fortunately, I discovered it in time before the car was driven a significant distance. The local Lexus dealer replaced it for free. This was not an isolated incident with the model... there are quite a few similar cases posted on internet forums. Why the Lexus dealer didn't recall and replace it earlier is a mystery. If you own this car or buy one used, make sure your mechanic checks all of the oil hoses! Otherwise, it's a great (if boring) car. We will pass it down to our teenage daughter soon.
This SUV looks great outside and stands up on the lot. Unfortunately, this is the only great thing about it. Very poor performance even after shifting into S-Sport. Car feels very heavy (like most luxury cars, right?) and lacking power. After taking it for a day drive around the town, I've got 22.5 mpg this is what you get for $19,000 used car (I was looking at regular RX for $9,000 and thinking: how much time/years will take to get the 5 mpg difference back?). Radio and controls are weird: like you are holding Japanese cassette player from the 80's. There is no way to find the button you need while you are driving... forget about using the joystick (awkward-est part #1 in this car ). So, bad gas mileage, mediocre performance... Probably good for people who cannot handle a V-6 engine (great for retirement?). I also tested LS 430 and I appreciated the ride (didn't buy it because we couldn't open a trunk. Later I found out that the car was overpriced).
Bought a 2010 RX450h from the Portland, Oregon Lexus dealer a month ago. We've taken it on several 4-hour trips and I've driven it every day on suburban roads with some freeway. Overall about 26mpg regular or premium, so we'll stick to regular gas in the future. I've noticed that I can nurse the mpg up to perhaps 28mpg by babying my acceleration and braking, but I prefer to drive in my normal fashion; anyway, gas is cheap and saving gas money wasn't the motivator. Pros: beautiful and luxurious. Surprisingly economical. Like a gorgeous woman who still loves tacos and beer. Minuses: Has middle-grade stereo, boomy bass at about 100Hz, (I'm an audio engineer, this really bugs me but what the heck), unknown future battery replacement cost (but other Prius hybrids have lasted for 200k+ miles, plus it's a Toyota/Lexus).
UPDATE December 2016: Now that it's cold outside, it takes ~10 minutes before the engine's toasty warm, and meanwhile the fuel economy is lousy. So if my trips are just 10 minutes every time, I get more like 22mpg. I would assume the EPA tests are done with a fully-warmed-up engine, which is why there is such a large discrepancy.
The great thing about this SUV is that the body changes so little each year that the car seems like new, at about a third of the price of a new one. I don't like the big new grilles Lexus has been making anyway, I think they cheapen the look. I prefer the more refined grille of the 2010. Despite that mine had somewhat high mileage, it was extremely well maintained by the previous owner and seems like new. I have had no problems with it thus far except I occasionally get a little carriage squeaking on overpasses for some reason, but not on regular paved road. However, otherwise, the ride is as smooth and quiet as silk. My favorite things about this car are the cushy interior and the high ride so that you can practically walk in and out of the car. No having to bend way down to get into the car. The quality of the interior is great, soft leather, nice wood on steering wheel and other locations. The only things that are cons for me are that the charger outlet and usbs are not in a good place. You have to remove a storage bucket in the front center console to get to them. It would be more convenient to have them in the dashboard area. However I guess it allows you to store things that are being charged or played out of sight. Heated seats are very nice. I like the auto lights and being able to talk on the phone handsfree via bluetooth connected phone. Mine is silver (tungsten pearl, to be precise; it is a little different than silver, I've noticed) with black interior and some light gray around the window area. I love it. Sometimes after I get out of it and walk away, I look back at it just to admire it. I am getting good mileage, averaging about 29 mpg thus far, and that's on 87 or 89. By all means, buy the luxe car a few years later at a fraction of the price!