I NEVER book flights with third party vendors, just the airlines.
First, I check Kayak.com for flights, the book with the airline. Sometimes there are cheaper options with vendors or even an airline (that I don't wish to use). I use Delta unless the difference in cost is significant.
Second, I book whole tours with tour companies like Gate 1 or others if that is what I wish to do.
Third, if we traveling on our own, I book B&Bs or hotel based on location, reviews and cost. I am with IHG for Holiday Inn and more hotels, so I may use them or my Chase card for points. Sometimes, I do use Booking.com if the price savings is significant over the hotel. Also, if I pick the Hilton hotel, I am with Hilton Honors and book with them.
For day tours, I try to book direct with the company, but sometimes with Booking.com or Viator.com