Vayne's biggest weakness isn't her weak early game, although she can be punished extremely hardly in her early game. Her weakness is that she has no ability to deal damage to anything outside of her autoattack radius. This means that against many champions, she will get into range of being damaged before she can damage them, and she'll often run into targeted ability range. Take annie for example, annie's q stun outranges vayne's autoattack radius, so vayne has major problems getting within range of her. Vayne is also very autoattack reliant, so champions like nunu and items like frozen heart are very effective against her.
Speaking as a Vayne main, here are some of the champions that piss me off the most:
Onhit stuns which outrange me and great burst, can zone me away from fights
All abilities outrange me, can't escape if she has rylais, in order to use my passive at all I'm vulnerable to her ult stun. Along with obscene damage.
2 Q dashes, movespeed increase, ult
Extreme ontarget burst which hits through invis.
Their ults make me cry.
Onhit stun, spears, good damage, blocks an autoattack. Noticing a pattern yet?
That stun has killed me far too often, those heals are a pain in the ass, and increased armor for every teammate? :c
Hurray for stuns that are up every 6 seconds.
...do I need to explain this?
I deal % HP damage. He stacks AP and keeps healing up any damage I deal to him. Also outranges me with every single one of his abilities.
All abilities on target which outrange me along with a snare for CC and gets damage from building frozen heart. ;-;
Ult. Movespeed slow. Attack speed slow. Lots of armor. Cri.
Those are just the ones that seriously piss me off as Vayne, there are a ton of champions which can deal with vayne effectively and kill her, it's just that they're slightly less reliable/I've learned to deal with them.