It does depend on where you are going.
The UK is not too big (compared to the USA) so it is not too important but generally if you are visiting London, I would go for London Heathrow, London Gatwick is good for the south coast or London, Cardiff is best for Wales, Manchester for the north west, Brimingham for the Midlands etc.
Whichever airport you choose, it is only a few hours drive on the motorways to get to somewhere else (except for Scotland of course where you really need to go to Glasgow or Edinburgh airports).
Personally, we usually use London Gatwick as it is about 70 minutes drive from our house. We have a closer airport at Southampton but it only has flights to a limited number of other countries.
If you are thinking of visiting anywhere in particular, I can offer more specific advice.