If you live in the north west I would fly direct from the north west. Just imagine if you'd booked to fly from Heathrow a couple of weeks ago when there was all that fog and yet you could have flown from Manchester no problem. Each change just makes for more things that can go wrong! Also, when you're flying home there's nothing worse than landing after a long flight, you're knackered and want to go home yet you've to wait for another flight before you can go home. If you fly via Amsterdam it's going to add hours onto your journey time, is it really worth it?
I have flown with Virgin to Florida from Manchester, and yes, it was a good flight, however I have also flown American Airlines to Chicago and Continental to Newark (New York) and found them very good. I am off to New York again in a couple of months and am flying direct from Manchester with BA.