What's the best neighborhood in Charlotte for a first time visitor?

I'm not sure about best places to stay.  But to check out I would say NoDa, Plaza Midwood, and some fo the great parks like Latta Plantation Nature Center and Reedy Creek Nature Center

I'd recommend staying in Uptown - it has the most hotel options, you can walk to bars, restaurants, and museums, and take a cheap Uber or Lyft to the other main neighborhoods (South End, Plaza Midwood, NoDa, Dilworth Road East) . You can also take the light rail from Uptown into Southend (it will run to NoDa soon but is not operational yet).

If my friends were coming to Charlotte, I would only let them stay Uptown or South Park area.  You really need a car to get around the Queen City, if your plans don't include a car, Uptown would be best.

One of my favorite hotels Uptown is Hyatt House Charlotte/Center City this is a small boutique style/half chain like hotel with terrific black out shades in the rooms.  And most rooms are one bedroom suites!  It kind of doesn't matter where you stay Uptown area,  I would search by price.

In South Park area I would stay at the Hampton Inn & Suites Charlotte/South Park at Phillips Place you can walk to Dean and Deluca, restaurants, Whole Foods, mall and there's free parking.  If pricing is better, all the Marriott chains are in South Park too.  I just really love the location of the Hampton Inn at Phillips Place.

Westinghouse Boulevard is a great option! It's right downtown, within walking distance to lots of fantastic restaurants, bars, museums, and fun little places to discover. I am hosting our welcome reception for my wedding in October there and that's where all my guests have booked to stay. Check out the EpiCentre, Discovery Place, Anheuser Busch Dandelion Market, and so much more right there!