Hotels have come a long way since my kids were little and we used to take our family vacations. It was my belief that the best way to take advantage of the hotel programs was to pick one and use just that one. I chose Hilton and it always worked for me. They are everywhere and easy to book. The Marriott also had a great program back then that we did use a couple of times in San Antonio and were very satisfied. Alas, I'm not up on the best chains or deals anymore because I just tend to use the "best deal" websites instead of honoring chains.
I think hotel chain loyalty, just like airline loyalty, does have its perks. Here is an article from Wisebread about The 6 Best Hotel Rewards Programs.