So lets say I have a target at -20 MR from my penetration items. Considering that %pen comes into affect after straight pen, would I then see from void staff an additional 40% increase to that negative value? (i.e. they are then at -28 MR)

I thought Magic Pen doesn't reduce MR below 0. Only things that say (MR reduced by X) will do that, e.g. Fiddle's Passive.

So it would go Void Staff > Archaic Knowledge > Runes > Items.

Well wait. "Penetration" and "reduction" and all that isn't what I'm asking about. I can get people negative with Annie and no pen runes just by stacking guise + abyssal + sorc boots. And %pen is always applied after any flat reduction.

But back to my question: if after flat reduction, I put someone in the negatives, will a void staff further increase that negative value?

No, but you are also doing your maths wrong. Neither flat penetration nor %pen can make an enemies MR go negative, nor will they decrease the MR of an enemy who is already negative.

Abyssal Scepter reduces MR by 20. Sorc shoes and guise each penetrate 20. Meaning if you have all 3 of these items.
An enemy with <20 MR will go negative
An enemy with 20<x<60 will go to 0
An enemy with >60 will have their MR-60

The %pen from void staff is applied after the -MR of abyssal, and before the flat penetration of Guise/sorc shoes. With all 4 of these items the following would happen
An enemy with <20 MR will go negative
An enemy with 20<x<87 will go to 0
An enemy with >87 will have their (MR-20)*.6-40 which will be >0

And for further clarity on this subject, %pens are additive not multiplicative, so with archaic knowledge it would be 55% penetration and the table would look like this.
An enemy with <20 MR will go negative
An enemy with 20<x<109 will go to 0
An enemy with >109 will have their (MR-20)*.45-40 which will be >0

In general you only want the abyssal scepter if you or a teamate has other -MR skills (Fiddle, Amumu, Ryze and probably some I am forgetting), otherwise flat penetration or % penetration is cheaper/more effective.

True, but the question still stands. If you get them into -MR (Fiddles/Amumus Passive, Exhaust, Abyssal, etc) what effect will %pen have?

I'm leaning towards no effect.

Correct, it won't do anything.

See my above post which says "Neither flat penetration nor %pen can make an enemies MR go negative, nor will they decrease the MR of an enemy who is already negative."

Alright, thanks. That answers my question about %pen.

Now I guess I'm wondering why does Riot differentiate between reduction and penetration? Why can only reduction take someone negative? Just seems kinda stupid to me...

It forces you to make the decision. You need to decide if the enemy is stacking MR or not. IF you could do %pen, then flat pen and take enemies negative it would get very OP.

That's not what I'm asking. Obviously having %pen first would make it the end-all choice. I'm asking why flat penetration can't take someone below 0 and why flat reduction can. They both lower MR at a flat rate, just doesn't make sense to me.