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We have had some great success with a few deals offered on our own site. for example the 10 Euro Vatican Tour offer which is valid when you purchase one of a few other tours at regular price you can get the Vatican for 10 Euro. We also have a "buy three, one goes free" deal. We call them our "crisis-buster" tours :)
link here: http://www.wheninrometours.com/Tours/Group-Walking-Tours/Vatican-Ci...
I use Kayak to research flights then go directly to the airline sites to compare and purchase the ticket.
I use Kayak and/or Fare Compare to get some preliminary idea about fares. I occasionally check with Vayama as well, but for some reason I haven't really gotten used to checking with them.
I prefer NOT to buy my tickets from a 3rd party site, much preferring to go directly to the airline. If anything goes wrong, I'd prefer to deal directly with the airline for resolution, rather than with a 3rd party. That said, I booked by Rome tickets through Cheap Tickets. At the time the savings was around $300-ish per ticket, so that clinched the deal for me.
For hotels, I used Hotwire.com if it's a city that I'm familiar with (I will know what hotels are represented by the opaque listing). If not, I tend to muddle around, and haven't really found a site that I love.