I've tried a lot of different Nasus builds. And after many games, and tweaking my build, I've developed this build.

Little Background:
I originally started with Nasus and bought recommended items. Didn't do so well, but learned how to farm SS

After a few games, and unlocking him since he wasn't free anymore, I decided to try to tank with him. I started doing really good, but I sometimes went negative by 1 or 2. And I usually had the highest assist count on the team..That's okay for some people, but personally I enjoy hearing "You have slain an enemy"

I learned of a "rediculous" build for Nasus from one of my friends. 6 Trinity Force Nasus. I thought "no freakin' way that'll work", but I tried it, and the first time I went 18 and 2. I had high kills every match with TrinForce Nasus. I would have kept with this build, but I realized that the passive (derived from Sheen) doesn't stack like the other stats from it do.

I started from scratch again, looking over what Trinity Force gave as far as stats. I focused on one at a time, and decided to boost those individually. For example: for movement speed/attack speed, I went with Phantom dancers. As they give better crit, better move speed, and better attack speed.

I kept working on this particular build, and now (although not as many kills) my kill-death ratio is much better. And I get assists a lot as well. I have gotten multiple aces, and triple/quad kills (would have had a pentakill but a Vayne came out of nowhere and stole it)

NOTE: Many people may not like this build, because they prefer Tank Nasus or other builds. And some may not like it because they can't pull off the Q farming/item building. If you do have a reason that you dislike this guide, feel free to downvote it, but if I may ask, please add a comment as to why you downvoted it (Comment for up-votes as well :) ) And BEFORE downvoting this build, at least read through the entire guide. Things may make more sense after a full read-through rather than a quick skim to see items/masteries/runes/etc.

Armor Penetration, Cooldown Reduction, Dodge chance, and attack speed are the primary runes that I use for Nasus.

Armor Penetration Marks: I use these to make regular attacks, as well as siphoning strike hit much, much harder.

Cooldown Reduction Glyphs: Makes siphon strike almost spammable, meaning more and more last hits. Ensures that your Ultimate should be ready or almost-ready for the next team fight.

Dodge Chance Seals: This, along with Ninja Tabi, make Nasus very, very difficult to hit. These runes can save your life, especially when running. There have been many times where I am running from a champion (let's say Ashe) with very low health. I get to my turret, and that last arrow comes flying at me, and it misses. Very helpful to be able to dodge attacks.

Attack Speed Quintessences: Increase attack speed, along with the cooldown reductions, a farmed siphon strike, and a popped Ultimate, make Nasus hit like a friggin' Octopus. Very fast, multiple times a second.

These are just my personal choices for runes, if you want to use different ones, more power to you.

Go for defense masteries primarily. Utilities as a secondary.

For Defense:
Hardiness, Resistance, Evasion, Nimbleness, Harder Skin, Defensive Mastery, Veterans' Scars, Ardor, Tenacity

Hardiness: Increases base armor. Keeps you alive through the game. Gives you the added defense that is needed against physical champions. Not a huge armor boost, but is worth it.

Resistance: Same thing as Hardiness, but for Magic Resistance

Evasion: Increases dodge chance, need I say more? Well I will. Makes it harder to hit you, keep you alive, kill more, or run away.

Nimbleness: Increases movement speed after dodging an attack. With a really high dodge chance, this will keep you moving fast. If you're running away, you'll dodge an attack, and increase speed and get away. This'll work for chasing someone down too, if they turn around and try to slow you or something, you'll dodge and catch up to them.

Harder Skin: Just to get further down in the Mastery Tree

Defensive Mastery: Same thing as Harder Skin

Veterans' Scars: Obvious reasons, keeps you alive.

Ardor: Increases Attack speed and Ability power. Attack speed helps you so much with this build. Ability power bonus is okay, but personally doesn't matter to me.

Tenacity: Decreases ALL damage done to you by 4%! Awesome, will keep you alive and keep your health up pretty decently.

For Utilities:
Spatial accuracy, Good hands, awareness, and greed.

Spatial Accuracy: Get this because you're going to be using teleport, this helps a lot.

Good Hands: Reduces time spent dead. There are some times when this will help a lot. If the games looking bad for you, you're team got aced, and the other team is attacking the nexus turrets, this can save your team. You respawn, pop ultimate, lay down spirit fire, and charge in.

Awareness: Let's you level up faster than other people, putting you at an advantage. Let's you get ultimate before the other players, which will help you get kills early.

Greed: Extra Gold? It may only be 1 extra, but it will help. If you're waiting to buy an item and you just need 10 or 15 gold. This 1 extra gold will make it come faster.

Items are the foundation of a good build. Without items, you'll never reach your potential!
First off. BOOTS! Then upgrade them to Ninja Tabi ASAP. Gives you much needed speed, and dodge chance. By now you'll see why the dodge chance runes and things come in handy.

Next, start building Phantom Dancers. Increase in movement and attack speed, really good when paired with the next item.

Infinity Edge: This will benefit you so much. Makes you hit much, much harder. Paired with a pumped syphon strike, this will do major damage!

Black Cleaver: Don't really have to explain this one.

Tiamat: Makes your attacks splash. Use this on a mob with Spirit Fire for some quick mob kills.

Lich Bane: Benefits of Sheen, just major upgrade.

Warmog's Armor: This is a conditional item. With the above item purchases, you'll get Warmog's Armor way later in the round. If the round lasts this long, this item will make the other team hating your guts. Poppin an ult with this item is great in team fights.

Siphon Strike first. Start building this up fast and early. Only hit enemies with low health to farm.

Spirit fire: Will help farm mob early. And it can harass enemy champions, most of the time resulting in them blindly chasing you, or running away to escape.

Siphon strike again, then get wither. By this time, you may be able to hurt, and possibly take down some enemy champions. Use this to give you the upper hand.

Basically from this point, Max out Siphon Strike first. Max the other two according to how the round is going. Of course, put a point in your ultimate everytime you're allowed.

Clairvoyance and Teleport

Nasus eats mana very fast, ESPECIALLY early game. Having this will keep you in your lane longer early game. Mid and late game, this will help you do all sorts of things.

Teleport can get you back to your lane quick. Or get to a team fight quickly. If still in a lane, you can /b/ back to town to buy something, and then teleport right back so nothing goes wrong.

Pros
Good Survivability
With well farmed Q, massive damage
Attacks fast
Hits Hard
Difficult to hit
Ultimate makes Nasus a very powerful Tank

Cons
Squishy early game
If not built right, very easy to kill
Nasus is easily focused on
Horrible against Ranged Champions

Buy the boots, head to your lane. Once the mob comes, sit back and farm your Q. (Stand Back and wait until enemies health is low enough to kill with siphon strike)
If an enemy champion comes, keep your cool and keep farming your Q. (unless they full out attack you, then fall back to the tower :) )
Try to build items as much as possible. Keep farming your Q, utilize Spirit Fire to bring enemy health and armor down.
Note: DO NOT Tower Drive until you get Ultimate. It may be tempting, but take the extra time to keep farming Q.

*You're probably getting sick of hearing to Farm your Q. Believe me, it pays off in the end.*

You should have Phantom Dancers, and Infinity Edge at least by now.
You're going to be doing a lot of damage now, especially if you got Siphon Strike Souped up.
You can start to wander around the map now. Run from lane to lane, where they need help, or where there's no one there. Kill a lot of mobs, (Spirit Fire should kill mobs by itself by now) and help with Enemy Champions. You're probably gonna get a lot of assists, and not a lot of kills at this point. Don't Worry, Late game will help with that.

You have the best items by now (with or without Warmog Armor, only exception :3 )
Now start driving into the other teams base. Lead the charge. Spirit fire, Tiamat, and a farmed Q will eradicate lane after lane after lane of monsters.
Don't use Ultimate at the beginning of a team fight, or even a 1v1 fight. Wait until you've done some damage to the enemy, so you'll be sure to kill them.

*If you're team is being dominated, fall back and play defense and have your teammates charge one lane. Nasus is a very good defender with this build.

*Always try to lead the charge. Act as the initial tank, then when/if you take a lot of damage, fall back and give the main tank the enemies to kill.