This is hard to say without sounding like a dick but I would go where my interests take me. Seeing a bunch of 'historical stuff' will be pretty boring if you don't know or care why it's significant. If you're more of a sensualist, travel accordingly.
Book online for popular museums and restaurants.
That's good advice. We're not going to see certain sights just because we're
supposed to see 'em.
For what it's worth, my undergraduate degree was in European history (haha) and my wife's was in art history (and she considers herself to be an "artist" as well)

so i've gotta take her to the great museums of Paris, Amsterdam, Madrid, Florence etc. Plus my wife's a big Catholic and so I definitely have to take her to the Vatican and the Sistine Chapel . . .
But I agree, it's best to have some flexibility in where we go and what we do. I might be able to make the trip 2 months long (i'm gonna be in between jobs) which will allow for more off the beaten track stuff.