Flight and hotel reservation systems have always been frustratingly complicated. It actually helps a lot to be a software engineer when you're trying to navigate the mainstream reservations web sites. It always seems way to hard to find what you're actually looking for.
If you share my impressions of those web sites, I recommend checking out Hipmunk. It's the first such web site I've ever used where my reaction was a smile of appreciation, instead of feeling an incipient headache coming on. So far, at least, they only have flight and hotel reservation – but those two things are done beautifully. There are lots of features about those sites that I like, but I'm going to call out two in particular that really, really resonated:
First, by default (you can change this) flights are presented to you sorted by “agony”, with the least agonizing flights on top. What do they mean by agony? It's a combination of price, layover time, and number of connections. I'd say that's a pretty accurate reflection of my agony index! In every trial search I made, the flights I'd pick were right at the top of the list. Perfect.
Second, when you're looking for hotels you're presented with a map of the general area, very much like a Google map view. A selector allows you to overlay one of several “heat map&rdash;. These show things like tourist attractions, shopping, nightlife, and ... “vice” (bars, casinos, and other adult entertainment). The result is a beautiful and simple way to choose a hotel by its proximity to what you care about. There are also very simple filters so you can see just the cheap hotels (or the expensive ones), just the ones with breakfast, etc. But those heat maps are just perfect – simple, visual navigation of what you can choose from.