Its all about the codes and the flexibility. I was a full Kayak believer (well until a few months ago when Kayak started getting fritzy and not giving real time responses for all airlines) but the search options and functionality of the matrix (which ive only scratched the surface of) is the best by far. I just had to book 10 r/t flights for business to diff cities - not only was I able to ensure that I paid the cheapest price, but I was also able to figure out which award flights (on Jblue - I had vouchers that were expiring soon) were "cheaper" to me based on their current pricing (not in a ppm sense but in a straight value sense. If flt 1 is $100 and 1,000 points and flt 2 is $120 and 1,000 points, which one do you pay for/which one award etc). Also I prefer to fly out of LGA over JFK but will fly JFK/EWR if the price is right. Its a lot easier to compare and sort airports/flight times with ITA. Orbitz doesnt really let you play around.
If youre booking a trip and your dates and airports are set in stone, by all means go to orbitz