I have always used Armor penetration while a lot of other people use flat attack damage runes.

I have actually no idea which one is better by statistics, so lets calculate!

Data lvl 1
Average amount of base AD for an AD carry at lvl 1 = 55
Amount of AD gain from masteries: 3 + 0,58/level = 3,58 AD at lvl 1
AD runes grant: 0,95 AD each mark and 2,25 each quint
Armor penetration runes grant: 1,28 ArP each mark and 2,56 ArP per quint

The minimum AD at the start will be 55 + 3,58 = 58,58 AD


Comparison lvl 1
Full flat AD
The one with full attack damage marks has the following amount of attack damage at the start:
58,58 + 0,95*9 + 2,25*3 = 73,88 = 74 attack damage.

Let's say the enemy has an average of 19 armor, 19 armor blocks 16% of the physical damage income.
Though, we have masteries, that also ignore 6 + 8% of the armor.
So 19 * (1-0,08) = 19 * 0,92 = 17,48
17,48 - 6 = 11,48
11,48 armor blocks 10% of the damage income

So each attack you will do 74 * 0,897 = 66,4 = 66 damage at lvl 1

Armor penetration
The amount of AD you will have is 58,58.
The ArP from your runes, will pretty much grant you 100% armor penetration, since:
1,28 * 9 + 2,56 * 3 = 19,2 ArP and the enemy has 19 armor.
However, we also have masteries that grant 6 + 8% penetration.

So we have the following from just masteries:
11,48 armor, just like in the previous chapter.
11,48 - 19,2 = -7,72

-7,72 armor actually increases the damage output by you.
The amount of bonus damage gain from -7,72 armor is 7,2%, which isn't bad,

So let us calculate the amount of damage each auto attack:
58,58 * 1,072 = 62,8 = 63 damage each auto attack

Conclusion lvl 1
Flat AD grants more early game power than Armor penetration.
Now let's look at lvl 18, while having full items.


Comparison lvl 18
Full flat AD
Your flat AD from runes and masteries remains the same.
For it is 0,95*9 + 2,25*3 = 15,3 AD
Now let's add the AD per level from the masteries and the champion aswell.
As champion I pick Tristana, because she is one of the most basic ADC.
So now we have 15,3 + 46,5 + 3*18 + 0,58 * 18 = 126,24 AD

I am a good boy and I listen to the top guide of Mobafire, who recommends me to get:
Berserker's Greaves, Infinity Edge, Phantom Dancer, Last Whisper, Bloodthirster and Mercurial Scimitar.

That grants a total bonus AD of:
270 AD (assuming that you have all stacks of the Bloodthirster)
270 + 126,24 = 396,24 Attack damage at lvl 18

The amount of armor penetration in flat numbers is 6 from the masteries, and thanks to Last Whisper, we now have 35% + 8% = 43% armor penetration.
Now, we are going to assume the impossible and say we face an another Tristana which exact the same runes, masteries and items.
The amount of armor she has is 15 + 3 per level, so that is 15 + 3*18 = 69 (LOLZ 69) armor.
The amount of armor that remains after penetration 69 * (1-0,43) = (69 * 0,57) -6 = 33,33 armor

33,33 armor blocks 25% of your physical damage.
So let's multiply:
396,24 * (1-0,25) = 396,24 * 0,75 = 297,2 damage each auto attack.
This excludes the chance that you have to make a critical strike, for the chances are the same with the ArP build, and the difference is minimal.

Armor penetration
We still have 19,2 ArP from runes and 6 + 8% from masteries.

The amount of AD we will have at lvl 18 with these runes =
396,24 - 15,3 = 380,94 attack damage.

We now, just like the last build, also have 35% armor penetration from the Last Whisper.
We are still up against a Tristana, which has 69 armor.

How much armor is left after penetration?
(69 * 0,57) - (6 + 19,2) = 14,13 armor remains
14,13 armor blocks 12,4% of the physical damage output.

380,94 * (1-0,124) = 380,94 * (0,876) = 333,7 damage output

Conclusion lvl 18
ArP grants a much bigger advantage than flat AD runes at lvl 18.


Overall Conclusion
The difference in damage output with auto attacks at lvl 1 is small, with flat AD having a bit more.
The difference in damage output with auto attacks at lvl 18 is a bit bigger, with ArP having more advantage.

However, the results of the ArP was calculated against an low armor ADC. Against tanks, it would make much less difference, making ArP and flat AD pretty much equal at late levels.

The more armor the enemy has, the less effective ArP is.
So keep focussing the low armor enemies with your ArP runes and you are good to go! :D

Good luck on the battlefield!
-Meiyjhe