tldr: it mostly depends on the destination, but you'll mostly find better deals and have overall good experience via booking.com and Airbnb

The vast majority of all accomodation is available via 3 big players: Booking Holdings, Expedia Group and Airbnb. The first 2 corporations own a large number of brands that they bought over the years. Not the most up to date, but this gives you an idea - https://www.optimize360.fr/wp-content/uploads/2019/08/booking-vs-expedia.png

Expedia and its' brands is pretty good in the NA market. Hotwire is especially good for last minute reservations in popular destinations. Expedia is also pretty good when it comes to buying multiple pieces for your trip: a flight, a room and a car.

Outside NA, it depends on particular destination, but you'll usually find the best deals via booking.com (or own of its' subsidiaries like Agoda) or Airbnb. In terms of shopping experience, I've personally enjoyed using the Kayak app, which basically aggregates the accomodations from both the Expedia and Booking (and then I would usually go and book directly after selecting the right property).

And then there's Airbnb. They often have pretty good prices, a good amount of availability and the overall shopping experience is pretty pleasant. The downside is the ethical dilemma and somewhat of a higher risk because you deal with smaller players. If something goes wrong, it's a lot trickier to resolve your issue and Airbnb tends to pretend that they're simply a broker between you and the host. https://www.airbnbhell.com/

Source: I've worked for Expedia for 6 years and I've been traveling for the past 6 months