This is a build that focuses on high damage with some survivability because Nasus is naturally bulky. With this build I fought a Tryndamere 1v1 and killed him easily. I also took a Mordakaiser to the face and won. So, before continuing, if you want a tank build, this isn't the one.

Before I get started, this guide is intended for 3's. I might make a 5's modification later.

Thanks for the comments. I really do take feedback seriously. :D

EDITS
9/5/11 - Changes made to build and rune explanation.

Pros

Excellent Farmer
Naturally Bulky
Carries Well
Unstoppable Push :D
Viable Jungler
Epic slow
His voice is awesome

Cons

Weak early game
Mana hungry
Very little CC, No strong CC (Stun, Silence, Taunt)
Difficult to get used to

Ok, to tell the truth, I'm guessing on the runes, so please give me some feedback here. I guessed the runes based on what I see as Nasus's early game drawbacks.
1 - He's mana hungry
2 - His natural MR sucks
3 - He doesn't do enough damage until he gets sheen.


Greater Mark of Desolation - Armor Penetration Marks

This is an AD build, so I shouldn't have to explain the importance of Armor Pen. marks in his rune page.

& Greater Seal of Replenishment - Mana Regen Seals

Nasus is a bit mana hungry, which is why this build originally had a Manamune in it. But then I finished these seals and suddenly I had no more mana problems.
But why 5 flat mp5 and 4 mp5/lvl?
I was thinking about this and the 9 flat allows for sustainable mana early game (during laning) but dies out late game. But, 9 /lvl doesn't give much during laning but you never run out late game. So, whats the perfect balance. 5 flat and 4 /lvl.

If you find yourself having very few mana problems or choose to get either Manamune or Chalice of Harmony, Greater Seal of Armor would be another good choice. These would also be the runes to get if you wanted a more tanky Nasus.

- Magic Resist Glyphs

Like I said earlier, his natural MR sucks, so get some rune for it.

- Attack Speed Quints

I was really confused on these for a while (and still am a little because I don't have them yet), but I narrowed it down the the fact the Nasus need more damage output prior to getting sheen. So, this allows him to do that while also making him more sustainable in lane because of his built in lifesteal (more attacks/second = more health healed)

Alternative Quints

Greater Quintessence of Desolation - Armor Pen
These quints are amazing. So, if you think attack speed quints suck, go with these for results throughout the game.

- Attack Damage
I personally think that Armor pen will have a longer lasting effect, the small amount of damage these offer dies out very quickly.

I only put 5 items in the build order because it's always good to have an alterable item or 2. So here are some good items depending on what you need most.

I'm currently testing some recommendations, this section as well as the standard build will most likely undergo some changes.

Attack Damage

- Yes, another on of these works. More damage, more lifesteal.

- Damage, crits, crit damage. Good if you like crits :D

- Health, damage, PERMA-SLOW!!!

] - I know this item gives no damage, it gives effective damage through 55% attack speed and 30% crit chance. This item isn't my style, but it's the staple of the AD carry. If you plan on getting this though, also purchase Infinity Edge at some point.

- Damage, crits, crit damage. By this in tandem with phantom dancer for 70% crits (15% trinity, 30% phantom dancer, 25% infinity edge).

Armor Pen

- One of my personal favorites. Damage and attack speed helps Siphoning Strike damage. Plus, you can shred more of their armor.

- More armor pen than Black Cleaver, but less damage and no attack speed, still a good item though.

Tank

- Great item. Health regen, magic resist and move speed is amazing.

- For those right clicking melee champs, watch as they die from being near you. The extra health and armor helps too.

- Magic resist, health, mana, and a spell shield. Great item to pop that Stun/Taunt/Fear that gets you killed every time.

- Armor AND Magic resist. Plus, just when they thought they killed you, you're alive again whacking their faces in with your staff.

- Health, armor, slows, and more slows.

This passive is incredibly convenient throughout the entire game. If you're jungling, it keeps you alive longer, and if you're laning, you're more sustainable.
Lifesteal Amount: 14/17/20% at lvls 1/6/11

Nasus's bread and butter. Buff's your next attack with bonus damage and every time you get a last hit with it, it permanently gains 3 damage. Early game this should be used for last hitting and an occasional harass on the over-extended melee champ. IMPORTANT - Siphoning Strike Works on turrets, inhibitors, and the nexus. This is what makes Nasus such a good pusher, use it whenever you can late game.
Cooldown: 8/7/6/5/4
Mana cost: 20/25/30/35/40
Range: 300 (About melee attack range)
Damage: 30/50/70/90/110 (+ 1.0 Attack Damage)(+ 3 damage per last hit)

Epic slow. Target and enemy, slow them for 5 seconds and as the slow persists, they get slowed more. Use this in team fights, to chase down the runners, ganking, and everything that involves an enemy champion. Also slows attack speed.
Cooldown: 15
Cost: 100
Range: 700
Slow: 35% plus 3/6/9/12/15% per second
Duration: 5

Farming + Armor reduction + Damage? Yes. Spirit fire is used for everything except attacking turrets. Farm with it, drop it in a team fight, and maybe getting that last tiny bit of damage in before they escape.
Cooldown: 12
Mana cost: 70/85/100/115/130
Range: 650
Initial Damage: 55/95/135/175/215 (+ .6 per Ability Power)
Persistent Damage: 11/19/27/35/43 (+ .12 per Ability Power) per second
Armor Reduction: 20/25/30/35/40
Duration: 5

Health, AoE DPS as a percentage of their max health that gets converted into AD for you. This ult is awesome to say the least. Use it in a team fight to hurt those melee champs that are stupid enough to stand right next to you. Tear apart those tanks that taunt you after you activate it. And best of all: You're low on health and you see Karthus about to ult, pop your ult and boom, the extra health just saved you and now Karthus Doesn't get an easy 20 stacks of Mejai's Soulstealer. :D
Cooldown: 120 at all levels
Mana Cost: 150
Radius of Damage: 350
Bonus Health: 300/450/600
Damage: 3/4/5% (+ .01% per Ability Power) of targets max health per second
Conversion of Damage dealt to Damage gained: 6.375%
Duration: 15

This build focuses on damage so, you want to put a point in Siphoning Strike whenever possible. Once you get Sheen, Siphoning Strike adds 200% of you attack damage whenever you use it. Get your ult, Fury of the Sands, whenever you can: it's awesome. Spirit Fire is next priority but make sure to grab a point in Wither at lvl 4 for the awesome slow.

I can't even count the number of times Flash saved my life. Not to mention how useful it can be in chasing down someone with a built in flash like Ezreal or Tryndamere. Exhaust is always useful and even more so with the mastery point in it.

Alternatives

Good spells

Ghost - Another great chasing/running tool

Ignite - Might just help you get that first blood you needed

Not-quite-so-good but still viable spells

Clarity - Helps if you don't have the seals, useless if you have them

Fortify - Give this to the real tank

Cleanse - Might save your life, but flash can help you get kills and save you

Heal - I never found this spell to help me much. Plus, Nasus has built in lifesteal

NEVER USE THESE ON NASUS

Clairvoyance - Give this to the support

Rally - It might help early game, but then it's useless. Nasus is a godly pusher without it

Revive - No, just no. Never use this. EVER

Conditional

Smite - Only if you want to jungle

Teleport - Maybe if you really need to get to another lane instantly. Whenever I have this spell, I forget I have it

Ok, I shouldn't need to explain this, but I will. Nasus is an amazing farmer/pusher.

Use Spirit Fire so it hits both the melee and the caster's. Siphoning Strike minions at low health to get the last hit: THIS IS IMPORTANT. Nasus gains damage on Siphoning Strike by getting last hits, so do it.

Jungle Nasus is viable; however, I'm still working on masteries/path for an efficient jungle. I'll post the new build with this one when I have it finished :D

Since this guide is intended for Twisted Treeline (Nasus's skill sequence changes for Summoner's Rift), I think it's important to understand the buffs available and when to take these buffs.

Lizard Buff
Wraith Buff

This buff gives:

• 30% increased movement speed

Wolf Buff

This buff gives:

• 20% Attack Speed
• 10% Cooldown Reduction

Dragon Buff