We have done Las Vegas + New York, for my 30th birthday, and it was a fantastic trip.
We didn't hire a car - if you don't mind walking, you can walk up and down The Strip quite easily, it's very flat, and obviously there is so much to see!
We did a helicopter trip out to the Grand Canyon, but obviously, if you wanted a couple of nights there, you would have to hire a car.
There are loads of hotel choices. We went at Superbowl weekend when apparently everyone goes to LV just to bet on the game! It was packed, and we couldn't get in any of our first choice hotels, but we stayed at The Mirage which was really nice, and in a very good spot just opposite the Venetian.
Depending on when you go, there are loads of deals to be had - you can sign up to receive them from the hotel websites. One piece of advice I would give is that there is so much to do and see that you probably the least awake time in the hotel you stay at, and more time in the others!
The Wynn is supposed to be a very special hotel - it wasn't open when we went, but I've heard excellent reports about it from friends who have been.
Other than that the Venetian and the Bellagio are beautiful - but like lots of hotels in LV, they are absolutely massive and very disorientating inside.
We flew back to NY for our last few days which was great because it broke up the trip home nicely and there are plenty of direct flights between the two.
Good luck with your planning, and let us know what you decide.