If you are going for comfort and good mpg, you won't get much better than a Toyota Camry Hybrid. While not considered a luxury vehicle, it has a plush, boring ride like you describe, and can be optioned out with luxury features. People get low to mid 40s out of it. The 2013 Avalon is basically a luxury Camry and will be offered with the same engine and hybrid system, which implies a similar 40s mpg.
The Audi A3 TDI can get 40, although I have no experience and can't comment on the ride quality.
Lexus has a CT 200h hybrid that is good for 50mpg. Again, I have no comment on the ride quality.
When I was shopping for a car, I wanted good fuel economy (4 cylinder), agile handling, and a decent amount of power. I found the TSX yo be the perfect compromise between all of those things, although the ride is harsh due to the sporty nature.
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