I believe with your focus on dining and gambling the Aria/Vdara/Bellagio area is a great central home base. I personally like Vdara an awful lot. Easy walk to Aria, Bellagio, Cosmo. Usually the least expensive of any of those yet still have amazing rooms.

V
 

I'd go with the Venetian. Lively, luxurious and a nice location. As far as a car goes, if you enjoy alcohol you better avoid driving. Las Vegas encourages drinking and it's easy to forget how much you've had.

Hotel recommendations for 50s something couple
 

Of the four you listed, I would avoid the Luxor, it's only a step above the dreadful Excalibur, IMO. MGM has a great collection of restaurants,
but with the exception of Mansions and Sky Lofts, the rooms are nothing special.

I'm hosting my wife's 50th at Aria next month, so I guess you could consider that my vote. Bellagio, Wynn/Encore (especially Tower Suites), Venetian/Palazzo, Four Seasons, and Mandarin Oriental are all worth consideration.

There's also a Mandarin Oriental in City Centre that is very nice, and close to Aria or Cosmo for gambling. If not that, Bellagio is always a good choice.