Technology and programming have improved a lot over time, it's getting easier and easier to do things like scripts undetected. It's not that it's impossible, but it's pretty difficult for the LoL program identify 'cheats' unless the third party program is directly manipulating the client.
The better technology is, the better the 'hacks' will become, it will probably always be this way.
That being said, IMO, there are some pretty obvious signs, but are only really noticeable if you're in the game with the scripter:
- Can easily dodge/land skillshots, but is pretty bad at everything else like cs'ing, build, positioning
- Dodges skillshots in awkward ways, dodging a skillshot but moving toward the direction of the enemy or under turret in the process
- When it comes to 'chases' in the jg, they are terrible, since a script cannot help them as much there
- Dodging skillshots when they have no vision
Before anyone comes in and argues this, yes a legitimate player could do all of these, but if they are doing all 4 of these it's probably a scripter.