Owned both. No problems with either. The Honda is nice but with fewer amenities than the Toyota. The Toyota is bigger, more powerful, rides better, and the transmission, no problems. Just leave it in "D" and forget about it. It has a gate shift mechanism if you want to be "sporty".
I think that Honda had some type of issue with their transmission in the past with the Accord and extended the warranty. I can't remember what years that was on but I'm sure they have that problem solved.
In normal driving you will get between 29 and 31 mpg using regular gas in the Avalon.
My wife drives it and this is her second Avalon (05' and now an 07') after the Accord.
If you tend to travel on long trips, the Avalon is superior IMHO, and the rear seats even recline. The Avalon trunk is very spacious as well, and a full size spare tire is stored under the deck.
IMHO, you get more bang for your buck with the Avalon, and your wife will love driving it.
Happy wife, happy life.
Good luck!