I have had two IS200's, and switched to a GS430 sport in september. I liked the IS, and was quite happy with mine. But, I wanted a more powerful car - and I was also becoming less impressed with the IS becoming so common on the roads (and the state of some of the IS's on the roads).
without a shadow of a doubt - the GS is a better car. I am very happy with mine, and when I get an IS as a courtesy car from Lexus - I am glad to get back into the GS. The IS is entry level Lexus, and the GS is next level up - and you can tell.
Its more comfortable - nice big leather seats, with a huge padded arm rest with loads of storage space in it.
its "nicer" inside - not as much black plastic.
of course its quicker - but you cant compare the 3.0 or 4.3 litre engines to the IS's 2.0. What is noticeable is how much more smoother and refined it is, and how subtley it puts the power down.
I had a GS300 for a weekend, and bough a GS430. Initially, in both cars I was quite inapproptiately speeding (45-50mph in a 30 )simply because its not so apparent that you are going that fast.
They are very quiet - you can cruise at motorway speeds, with a CD / radio on the background - and talk at a normal volume.
The downside is the suspension / handling. The IS does handle better than the GS. Yeah - you can change suspension compenents to improve it (as I am) - but you have to compare stock to stock. If you want to be throwing the car around bends, you'll probably find it doesnt take them as well as the IS.
I would strongly recommend you test drive one. Work out which model you are interested in, and get an extended test drive off Lexus. When I spoke to Lexus Chester, and made it clear I was a definite prospective buyer, I was given a GS300 for a whole weekend to test drive unaccompanied.
See what you think of it. If you have any specific questions about anything, feel free to post them.
Hopefully people like Claire, Colin and Brett will let you know their experiences of swapping models.