Because your AD damage is converted to True damage, any runes that would give you lethality (sudden impact) or life steal becomes less efficient with this rune. It is very counter-intuitive for most people since you think you would be investing in more damage/sustain with the secondary runes, when you actually aren't
PhearBunny6 votesless efficient doesn't mean useless. There are still matchups where youd go domination secondary.
DeadUnborn1 votesyeah, the real problem is the rune being counter-intuitive, not useless
This is a problem because it makes for weird, not straight forward optimizations, which Riot tends to avoid
Z3Sleeper2 votes...how is this an issue?
Your lethality will still linearly increase the physical damage you are dealing and not affect the true damage at all.
This is like saying building 
on 
is counter-intuitive because it doesn't increase her % health true damage.
Edit: All three of you below are missing the point. You are forgoing armor completely, thus you don't want lethality/pen in the first place. If you still need it, you can still buy it to increase your non-true damage. Champions do NOT need compensation for "wasted" lethality/pen stats.
Sasogwa2 votes...how is this an issue?
Your lethality will still linearly increase the physical damage you are dealing and not affect the true damage at all.
This is like saying building
Well it is less efficient than on a champion with no true damage. The cost-efficiency is less good on Vayne than on Jinx for instance. For the same gold, you get less value.
NemeBro1 votes...how is this an issue?
Your lethality will still linearly increase the physical damage you are dealing and not affect the true damage at all.
This is like saying building
It actually is counter-intuitive and her W in fact gives her incentive not to.
You ever notice that melee carries like Yi, Yasuo, and Fiora have tank-shredding mechanics in their kits to allow them to forgo building a LW? They have these mechanics because they aren't safe enough to justify building an item that offers relatively little overall damage (in the sense that it only substantially increases damage to tanks and bruisers) and no safety. Vayne, as the overall shortest-ranged ADC, is the same.
DeadUnborn1 votesSure let me explain:
Vayne's W is on hit added damage; Conqueror, on the other hand, CONVERTS part of your damage into true damage (which means life steal and lethality don't apply to the portion of the damage that is converted (not added).
A clear example of this is Vel Coz' rework. Before you would buy Liandriss for added damage. Now because most of vel Coz' damage is true damage, you don't buy magic pen items on him and instead buy CDR and AP
C9 Squeeky 1 votesless inefficient?
DeadUnborn1 voteswhoops, thanks!