Really good question.
I had an RX300 (2005) and now have an RX350 (2007).
In the RX300, I used to get around 23 mpg around town and 28 mpg on a 70-80mph motorway run. My around town driving is in West Yorkshire with a mix of roads, many of them hilly. Generally, I always got 250-260 miles on a brimmed tank.
In the RX350, fuel economy seems to be marginally better around town when driven with care yielding 23.9-24.0. On the motorway, it seems to be closer still to the RX300, but overall, I am getting more like 270-290 miles to a brimmed tank. There is also the advantage of having 270 bhp over the RX300's ~200 bhp.
What I will say is, both cars do seem to be sensitive to how they are being driven, though I never got anything worse than 21 mpg or 250 miles on a tank with any of them. I do try to be a gentle driver and plan my drive without having to step between brake and throttle all of the time, but then I am not stuck in bad stop-start peak hour motorway congestion every day.
Also, my experience with Lexus cars is that they tend to improve on fuel efficiency and power once the first 10,000 miles is over. I can only out that down to the engine bedding in more and loosening up.