How can I keep monsters out of my nether regions?

As of the Halloween Update:

You don't have to worry about Zombie Pigmen (they are, after all, neutral mobs until provoked).

Ghasts can safely be kept out by restricting yourself to not using any of the 4x4x4 (or larger!) areas that they need to spawn. Keep a tight ceiling, and you'll be fine.

Hehe, Withers and Blazes only spawn in certain locations, namely Nether Forts and between a height of 64-74 (ish, I do not have the exact values with me). The easiest way to get them to not spawn is to simply move out of the nether fort that you have set up shop in. The pigmen will be and always are a problem but if left alone they are just annoying.

If you are set on being in a nether fort though, then I suggest half slabs. Nothing likes spawning on top of half slabs regardless of how much space overhead you need.. Also keep in mind a Ghast loves to spawn in a 5x5x5 area. Having one of them appear in your house really really sucks.

Ghasts are the real problem; if you want to have large rooms, build pillars or let some blocks float in the air (not very handy). You can also make a trap with some dispensers to get some pork and gunpowder.