What aspects of her everyday life does your wife dislike the most? Make sure those are entirely absent from the vacation.
F'rinstance: If she doesn't like to cook, do not book a place with kitchen. If she does like to cook, but normally doesn't have time, let the kitchen feature prominently in your arrangements, and make sure there is a good grocery store within reach.
If she is normally stuck dealing with tangential things like arranging for a babysitter and getting someone in to water the plants, make sure you cover all those things too. If necessary, sneak a look at her passport and make sure it hasn't expired.
Check with her work and make sure you haven't planned the vacation for a week when there's something she absolutely can't miss, no matter how much she'd like to.
Bonus points if you can fool her with something preliminary like chocolates and flowers so she thinks Ooh, he remembered our anniversary! while having no clue that that's only the beginning.
Oh, and psst! Women like words. It doesn't matter if she knows perfectly well that you love her. Tell her so anyway.
Sounds like you're planning this together and you just need ideas of nice places to see. For my family, our vacations tend to fall into the categories of food, experience, and rest/relaxation.
Food Don't know what it's like for you and the missus, but for us good food is an important aspect of travel. It doesn't have to be expensive or white table cloth either. Some of my most memorable dining experiences have come from a cart in NYC and a tamale from a sleepy restaurant in Pecos, TX.
One way my wife and I enhance a trip is to give it a theme. On one trip to New York we did all the usual things but we also made a point to visit what was generally agreed on as the best or most venerated pizza restaurants in the area. We did the same for a recent trip to Texas in conjunction with BBQ.
Experience For us, nature, indigenous culture and historic areas provide interesting experiences. We recently visited Carlsbad Cavern and were in awe of the cavern, for us a profound experience. However later that evening we were moved by the emergence of the bats from the cave, listening to their fluttering wings in the desert silence and watching thousands upon thousands emerge from the cave. It was as close to a religious experience as I have ever felt. I'm sure it's not the same for everyone, but that's how it was for me.
An example of indigenous culture, we had the good luck of catching a national flamenco troupe that was touring through Cordoba, Spain. Another cultural event I enjoyed was Bread and Puppets in Glover, Vermont. I enjoyed visiting Graceland last week, that's more of a place-type experience.
Vacations for resting and relaxation Our rest-type vacations usually revolve around nature (woods and lakes), typically in a cozy and not rustic cabin that isn't necessarily isolated but definitely not overrun with tourists. Rural and quiet. But still within driving distance to a few nice/good breakfast and lunch joints.
So maybe thinking about the type of vacation you want, what you want to get out of it, then working your way outward from there may help get you to a starting point of identifying where you want to go.
Don't end up eating at expensive and poor quality tourist traps or get stuck in a fleabag motel in a sketchy or boring neighborhood because of poor planning. Wherever you choose to go, research places to eat, things to do, places to stay. But remain flexible to changing the itinerary should something unexpected and nice pop up. Planning is essential.
SniqueAway and VRBO are useful sites.
There are so many cool places to visit in the world and not enough time.
Damascus is a unique - and i've heard there are lots of cheap deals at the moment!
.... but that aside: if you are active Walking the Inca Trail is awesome. my own favourite holidays have been road trips in the states, hire a cool car from the Hertz premium range, avoid the interstate and just drive through places you've never been. A trip to Europe: London, Paris, Italian Lakes
what do you like though? activities? sitting relaxing? history? adventure?