The RX350 gets better gas mileage and can hold a lot of cargo. It's pretty zippy too in traffic. My wife has a 2017 RX350 and loves it. This is number 4 for her and her next car will be the same. 

I would not buy either one of those vehicles if you're buying used. When the repairs come in, it will be expensive. Used hybrids are out of the question because it will be an even more expensive repair when they break.

Do you plan on getting one used or leasing a brand new one?

Go with the Lexus RX350.  The V8 in the GX will result in a higher total cost of ownership as you rack up the miles, including worse MPG.

As for best years, see below:  2007 was the first model year of the RX350, but I would look at model years 2011 and newer.

https://www.motorbiscuit.com/the-worst-lexus-rx-350-model-year-you-should-never-buy/

Also, have a look here:

https://www.carcomplaints.com/Lexus/RX_350/

My mother owned a 09 RX350 and I have a GX470, pretty close to a 460. I drove my Mother's on some trips.

Both are nice vehicles, and very reliable. I would say that they are very different vehicles though.

The RX is just a great mid size suv, for getting you to your destination comfortably.

The GX is much bigger, gas mileage is going to be probably 7mpg worse at least, neither vehicle is great.

The GX has a full time 4wd system, aka awd with locking center differential. It is much better for towing, and nasty weather driving.

Just today I turn onto the street a friend lives on, and they on a super steep incline, I was going very slow. It is super cold and icy, even though I have winter tires, I heard one tire start to slip just a little, and the vehicle shifts power to another that had grip. It did that several times crawling up that hill, in a vehicle without awd and winter tires would not have been fun at all.

Both vehicles are reliable. You mentioned worry about the cost to fix a 460 engine, consider that is it one of the most reliable ever made. Many 470's have gone a million miles, and the 460's are following that tradition. The 460 also has a timing chain, so you don't have to worry about changing the timing belt at least.

The GX rides great, best I have ever been in, in any weather. I travel several thousand mile round trips many times a year, I would rather drive it, than the RX, but that rides well too, don't get me wrong.

I would suggest that unless you really need a GX, the RX would be a better pick. I have to tow, and always find myself in really nasty weather, I need the GX.