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In Manhattan, anything south of 96th St. is fine, and most things north are ok as well. In the outer boroughs, any area around a tourist attraction (Brooklyn Botanical Gardens, Museum of the Moving Image...) is good as well.
The bad reputation of NY is vastly overhyped, and mainly a leftover from the 1970s and the sensationalism of watching cop shows set in NY.
I would stay south of 96th st. Otherwise everything else is safe. All the touristy stuff is in safe areas anyway so you don't have to worry. Like stretch00 said, the tourists attractions in the boroughs are in safe areas as well. So unless you are going to do something that is non-touristy, I wouldn't worry about. If you want to go to Brooklyn, Brooklyn Heights is really nice and the Brooklyn Promenade gives you a great view of Manhattan - it feels like you can reach out and touch it.
I've been to NYC several times as a tourist and love it there. Any tourist area you'll be OK. I don't think I've ever felt "unsafe". The only thing is, you do a lot of walking and that might be an issue for your wife. We always took the subway so half of our walking might have been due to wrong turns so if you guys take the taxi or whatever tourist bus I see all the time around Times Square then you should be OK! I hope you guys have a great and memorable time together.
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