No travel website is perfect, but Expedia does a pretty good job. Their interface is easy, logging in with Facebook is easy, and earning rewards is easy. But most importantly, actually booking is easy. I like that Expedia accepts all forms of payment and makes it easy to book, unlike directly booking with many airline websites that reject foreign credit cards, don't accept American Express, or routinely flag purchases and cause problems.
Unless I'm booking travel within the US where I book with the airline or hotel directly, I always use Expedia and have never had a problem.