For domestic air travel I first try Mobissimo, a meta search engeine that searchs all the other sites and presents you all the results. You can rank order the results by price and by the time for the trip. I rarely am willing to take the 24hr trip if I can get there in 6 hours even if it costs less. Be careful about just getting the cheapest tickets. I also check fares and travel times starting from all 4 area airports. After seeing my options, I usually go buy the ticket directly from the airline web site.
Two airlines that serve our area, Southwest (Albany) and Jet Blue (Burlington) only do direct ticketing and their flights do not show up on any travel service or meta search engine on the web - you have to look at them directly.
For international travel I use Vayama to narrow down my options. It is the same sort of meta search engine, but for international routes. Where I actually buy the tickets depends on the route. Balancing the duration of the trip and the ticket price is your main choice.
For hotels in specific cities, I look at Trip Advisor, and read reviews of hotels by people who have recently been there. Some friends use Luxury Link a lot as a way to get last minute deals on pretty nice trips and packages. More recently, I use Google to search for "vacation rental apartments in xyz" and try to rent a place for our stay.
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