I faced exactly the same dilemma. About 3 weeks ago, I test drove a new ES330, and while it was nice and beautifully constructed, its performance and handling were lackluster. The dealer had a Certified Pre-Owned 2001 GS300, which only had 32,000 miles on it. It was in beautiful condition, and had been maintained well and just received the 30,000 mile service.
The driving experience was quite different. It handled much better and the 220 HP 6 cylinder, while not equal to such 6 cylinders as are in the Infiniti G35 or Acura TL, had plenty of acceleration. Also, it handled much better and you had more road feel. I did find it was slightly more noise, but the new tires put on by the dealer are a little noisy. Finally, the interior is understated but beautiful. The Certified Pre-Owned designation gives you a 3-year, 100,000 mile complete warranty plus Lexus' fine service experience. I don't think that the cost of tires, depending on what you buy, will be a major difference between the two cars.
I bought the GS300 and I am very glad I did. It has the best combination of luxury and comfort combined with sportiness that I have driven. If you go with the GS, make sure the 30,000 mile service has been done. I paid $29,000 even, which I don't think is too bad for the low mileage on the car and its being a CPO car with the warranty.