Easy answer.

If you have a travel and stay pattern compatible with a single chain, do it.

Otherwise, hotels.com.

My work blanket is pretty large and not well-supported by the major NA chains, as much as I like them. Hotel elite perks are trivial compared to airline. Higher floor? Like getting row 10 instead of row 20 in economy - big deal. Room location? You can talk into the same thing. Almost everyone provides free internet nowaways.

I have mid level status at a few chains places due to a combination of stays, CC affiliation, and airline status matching. Sometimes i do book directly with the chains esp at nice properties for better probability of upgrades and such.... But the status recognition, perks, upgrade %....virtually non-existent. (Get nice treatment at JW.M Ankara simply because i stay there often)

Worries about Protection in case of booking problems and other 3rd party vs direct vendor issues? Again, pretty much nil vs airline world

Wouldnt hesitate to recommend hotels.com to anyone