For mostly city driving, is it worth spending the extra money on a cpo Lexus hybrid suv or just get the rx350?

The great thing about the Toyota/Lexus hybrid system is city driving. The gas engine completely shuts off when coasting or very light acceleration. So often in stop and go traffic the engine doesn't even run. Bear in mind in weather extremes (hot and cold) the engine runs more to cool and heat but still, it does well. If you are looking at this from a purely CPO standpoint, go with the 350, you will (IMHO) spend more on the 450 with the upfront costs and calculating your benefits is sketchy at best, due to all the variables to consider. I have a 400h and have gotten as much as 36mpg for a tank of gas driving through the White Mountains in NH and VT. On this trip, I was driving around 40-50mph and not running the AC. I typically get about 26-28mpg commuting to work and 25 on the highway. The worst mileage I have gotten has been about 23mpg in the winter with the engine running a lot and some more aggressive driving. Still, I love the hybrid because for me, its about efficiency, not TCO ... when I am stuck in traffic or eating my lunch in my car, there is a value for me to not be consuming gasoline. Good luck!