Open ended question, I know...but I wanted to post some observations from a recent trip. I used Hotels.com when they had their 10 nights free program (which no longer exists) and the in past had used booking.com quite a bit.

The experiences seemed a little less 'nice' than they used to be....
1) Using booking, I booked a hotel in Istanbul for a week. It was a basic room with no real view (could go to the roof restaurant for that). Upon arrival, we were given an upgrade to a room on a higher floor with a view toward Sultanahmet. Turns out, the room was right below the restaurant so every night after dinner we got to hear them moving tables around at about 11pm and again at 7am while getting ready for breakfast. Not a great upgrade IMO.
2) In Ephesus again using booking.com, got a decent room but it was right over the lobby and the best view we had was the entrance to the hotel property (versus one with a view out toward the valley). Not a big deal, we weren't in the room much.
3) Used booking again for a hotel in Strasbourg. Got a 1st floor room facing an alley. Was really hoping for a higher floor room with a city view but was told they were full (I don't believe they were).

SOME of the direct hotel bookings I made (or with hotel points) were better than those experiences...as an example, the Intercontinental in Istanbul gave us a high floor room with a great view (using points and free nights).

I'm thinking about changing my strat to book directly with hotels/chains instead of using the travel sites. Anyone have any thoughts?