Travelling Apprehension

When I was younger I visited Colorado and some surrounding states with my family. As an adult Hubs and I have gone on cruises and visited a friend of mine in San Diego. We also visit Virginia Beach where his parents are. Last year I went to North Carolina for a conference. This year I'm attending the same conference in Portland, and I'm also attending a conference in New Orleans. 
All of those trips aren't hard in terms of planning. I've been with friends or family, or on a cruise or conference where many activities are curated for you to choose from. What gives me anxiety is taking a trip where no one I know awaits me. We're hoping to go to Hawaii next year, and I'd love to eventually make it to Italy. 
I get anxiety when I think about planning activities in a place I've never been where there is no one I know. I don't want to get caught up in tourist traps or scams. I want to travel around in the most efficient way. I'm also very concerned about looking too much like a tourist or doing something offensive to the culture of a location.
The first uncharted territory we make our way to, I'm sure will come with lots of Google research. 
Where have you gone? How did you plan for your trip?