GUNS OUT
When people think of POS defences, they think guns. Lots of guns. This isn't necessarily the best solution. While a good gun setup is effective at taking out Battleships, Cruisers, Frigates and all their Tech II equivalents, it's not so hot against Dreadnoughts. The issue is siege mode. A Dreadnought in siege mode is immune to Electronic Warfare and has an insanely large bonus to its tank.

When setting up guns, there are two main avenues of thought. A well-rounded setup including a mixture of small, medium and large gun arrays is a popular choice. The idea is to be able to destroy anything Battleship-sized or smaller. The downside is that it'll be pathetically weak against a Dreadnought and won't make a dent if it's in siege mode.

Another common tactic is to load as many large guns as the powergrid will allow. The idea here is to maximise the damage dealt to Dreadnoughts. It may have about a 50% chance to destroy one before it gets into siege mode and its tank kicks in. It can achieve a large amount of damage with Amarr towers and an absolutely massive amount with Minmatar towers, given their special bonuses.

In the past I have seen Frigate swarms fly around starbases to waste the ammo so that a larger siege force could come in unharmed. It's worth mentioning that a Frigate swarm would give any Dreadnought time to enter siege mode and turn on its tank, at which point they would be pretty much invulnerable to anything an unassisted POS can output. Therefore, I believe that the idea of fitting a large number of large guns is ineffective.

Some more effective methods of defence, in conjunction with a good, well-rounded gun setup, include heavy webbing, scrambling and ECM. Fitting a large number of webbers will make a Frigate fleet a lot less effective as they get popped by your small guns. The scramblers ensure they can't get away. ECM serves a useful purpose, especially on a Caldari tower. ECM modules have a guaranteed jamming rate on any ship, making them a very powerful but limited resource.

MAKE THEM PAY
It is my firm belief that the best way to defend a POS is to make it not worth the effort for the attacker. To do this, you need to first increase the cost and risk to the attacker. The first step is to force your opponent to have to use Dreadnoughts in siege mode. This is easily achieved by putting up a defence force that Battleships and smaller ships cannot stand up to. A mixture of small, medium and large gun arrays and webbers will work. Scramblers will force them to face the reality that any ship that goes in bar a sieging Dreadnought will explode. This combo is often enough to put them off. Add some ECM and you have a tidy setup.