Cbird here's a couple of sites that may help you .
http://www.sidestep.com is a site that my DW Jana used quite a lot, she thought they had some good deals.
http://www.orbitz.com and
http://www.expedia.com are worth checking as well, although from the UK Expedia may try to take you to the (more expensive) UK site.
The only major problem with booking an on going flight with another airline is that if your original flight is delayed/cancelled they have no obligation to get you on a later flight. If you are booked all the way through on one airline they will get to your final destination eventually.
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To the original poster/question
Susie, for your sister to fly to the US I've found that using
http://www.ba.com (which is British Airways website) it's much easier than most websites to work out if you change your plans slightly which days of the week or times of year are the cheapest to travel. You can request they give you flight costs +or- up to 14 days around your expected travel date, this can often allow you to make a huge saving by leaving/returning a day or two earlier or later. As has been said, avoiding school holidays and big times like Xmas and Easter would be the most likely time to get cheap flights. Other companies to check are
http://www.ebookers.com ( they also work under the name flightbookers) and to call Airlinenetwork who advertise in the UK newspapers.
In general flights to New York ( in particular) and Boston to a lesser degree can be snagged for some very cheap prices if you don't mind too much which airline you fly with. Kuwait Airways and Saudia used to offer some great deals
but they don't serve alcohol on the flight , Air India, Malaysian and Singapore air also were regular companies that would discount quite heavily.
For choice (if costs was equal) , my preference would be American Airlines or USAirways for the size seats they offer, but if that's not an issue , I would look at British Airways or Virgin.