Once you've gathered the background information you need, use it to make decisions about what to see and do.
Seek a balance. Whether you love art, people watching, canoeing, or military history, if you plan at least part of your trip around your interests, it's hard to go terribly wrong. Conversely, try to include some things that seem beyond your usual experience. At its best, travel expands your horizons without overwhelming you.
Make a list. Write down all the sights and activities you want to experience. Be careful not to pick something just because it's there (that approach has turned even Mount Everest into a tourist trap!). Choose instead what you really want to see, according to either what you enjoy or what intrigues you.
Prioritize the list. Choose just a few must-see items--the things you'd feel deprived of if they weren't part of your trip. These are the hooks you can hang your itinerary on. Next, decide on a number of alternatives, or "would-like-to-sees." You can fit these in, or not, as you go along. The idea behind prioritizing is to spare yourself the stress of frantically trying to see "everything" (which you'll never be able to do).