There's a bunch of cool combinations which we probably won't see due to geographical locations or other circumstances, such as Gragas in a bar fight with Vi or Lux sympathizing with Annie. The coolest one I could think of would be Poppy and Nunu, since one wants to be a hero while the other wants to find one, maybe Nunu helps Poppy realize she's more of a hero than she thinks.
and 
"Ok?"
"Ok"
Either 
and 
Or 
and 
and 
and 
imma say it cuz someone has to
/ 
some men, just want to watch the world turn into a hent... BURN, watch the world burn.
and any creature from the void
and the rework system
my real answer would be 
& 
the 2sisters
Well ... I'd say 
and 
... Because POWER :D !
and for obvious reasons
and 
They are kind of related but not really. It is very possible for them to run eachother so I want see how it will turn out
Maybe soraka and garen, if she can somehow show him that his actions could lead to lux's death because of his hatred for magic, maybe he can have some cool character growth. Or maybe ryze and asol? That could actually setup further world plot development, maybe lead ryze to gather some allies in preparation for the coming of the void, since asol can't due to his enslavement.
this may seem crazy but 
and 
a kind hearted giant and a mean ass yordle. on a lizard. or maybe and
and
Syndra would have a lot to say about the restrictions Demacia has put on Lux and might try to show her the benefits of cutting loose/try to corrupt her.
Conversely Lux could see that although Demacias' fear of mages has gone too far, it's also far from unwarranted given Syndras' power and willingness to use it
and
Now here me out here. Ornn was Dorans teacher, right? Doran, at the peak of his skill, made a weapon that would be known as his greatest creation. that creation is the staff uses, as Yi (at least as far as I can tell as it still being cannon) got the staff from Doran and then passed it along to Wukong. So REALLY I'm not looking for an interaction between them, I'm looking for to comment on Wukong's staff, possibly wanting to take it to make some improvements.
Another one would be more for Easter egg reasons. and . In the old lore they were both from the Plague Jungles. pretty much just have Wukong say something like "hmm, I feel like I know that guy from somewhere..."
Idk but I hope when they VGU 
they don't make him acknowledge 
. It's kinda cringey when serious champs talk to her(like 
).
and Would be interesting to see.
And 
They both have sort of the same role but went different ways with it
x 
Id like to see what would happen if they combine knowledge
and 
My and my unbiased self;
Not sure what they would have to discuss, if anything, but I love them to death so it'd be neat.
Lot of potential for Rhaast to nag at them for being edgy.
You gave Irelia and Sivir an interaction, yet slept on my mans.
For all the Ez & Talon lovers/shippers. Dunno, this one could be neat as well I guess.
I'm so sad that Kass isn't getting any interactions. Anyway, Kass has explored a bunch of shit and still does for artifacts for combating the void. No way he hasn't snagged an artifact before Ezreal and there is no way Ezreal is not interested in this guy. Armor from Zaun (I believe), the Void Stone, Horok's Netherblade! And, with the loss of his daughter, having someone young and full of energy around would probably grow on him and help repair his 'I don't care unless I'm fighting the void' attitude.
Sandwraith Pyke, to be exact. Any Shuriman, honestly. I just love Kassadin.
"Noxians, I hate those guys." and, "Ninjas, I hate those guys." IT'S AN EASY, "You stole my line!" from Ezreal!
I know that these three are related but please Kassadin needs love!
Akali and Lucian
Yorick and Pyke, Yorick wants to help the dead of the Shadow Isles rest but Pyke isnt exactly the Black Mist variety of undead, or maybe Pyke and Illaoi, how would she feel about him still having an ambition as a revenant, or is it more of an unending obsession and she would consider him stagnated
and
They both kind of went against what their society saw as proper, and instead fight for that country/region/etc with their power. It would also be cool to see how Lux would react to Karma, who comes from Ionia, the literal magic land, and how Karma would react to someone who suppressed their gift for so long.
Also 
and 
Kindred has a reaction to Karthus, but I think Karthus, who practically worships death, should have a really interesting quote concerning the embodiment of death itself.
Talon and Irelia because they both use floating(?) blades and they would probably fight, but it would be interesting.
and
Mountain mover vs mountain Best of Friends
Swordsman of Wind, with Wind.. sprite? God? Wherever they left janna's lore at.
wink
&
I want to see what possibly could happen if Elise sees the most beautiful succubus of Runeterra, as she is the one who seeks eternal youth and beauty.
Preying on 
Talking with
Trying to help
Hunting 
Ranting at
Tricking 
Meeting 
Has an encounter with
How can this be so much fun.
and
My and my girlfriend's mains.
I have no idea how they would interact but I just imagine Nami blowing bubbles at Noc and Noc looking like "what did I get myself into."
and 
They're artists, kinda
and
"That's a big list."
and anyone of the following //
and anyone from the black rose ( 
) it would be interesting seeing the powerful intelligent immortal sorcerers and sorceresses have a conversation with the future seeing prophet of the void who's arguably as strong as they are in magic (or stronger)
I'd love to see lulu and gargar
