On my next long trip (from Minneapolis to Italy), I chose to spend about double for business class, because the prospect of 10 hours flying in economy literally terrifies me.
When I fly to Taiwan I make a point of traveling on Eva (a Taiwanese airline) which has a class between economy & business (like Virgin). It's well worth the extra cost for a 12 hour flight.
I would gladly pay a premium for exit row or galley seats with more legroom. I still don't understand why airlines don't consistently sell these seats in advance.
In years when I'm flying a lot, I always stick with the same airline. Getting elite status gives you free upgrades and first crack at some of the more comfortable seats.
All of which is to say that price & schedule are not really my #1 considerations.