Hi GTO. There is a microstakes streamer who I follow on YouTube. He is not at the standard of a RIO pro but he is a decent winner at microstakes. Anyway, the guy pure calls with AK vs a 3-bet from most opponents in the SB or BB when he is UTG or MP. Do you think this is ok as a default strategy?

With AKo I think its absolutely fine and it is what I personally do as well. The differential between flatting and 4betting in turns of EV vs optimal SB/BB 3betting ranges is so small (<5%) you can justify flatting out of personal preference. Versus players that do not 3bet enough OOP, flatter seems like the better line anyway since you have less fold equity and AK is technically your bluffing hand when you 4bet. But overall, using a mixed strategy with AKo is a strong play supported by theory.

However with AKs the EV difference between 4betting and calling very significant (>100%). I can't justify flatting and missing out on tons of EV, so it must be pure 4bet preflop.

After AA, the next best hand to put into your 4betting range is AKs. But your friend is probably playing an exploitative style where opponents just put too much money in with AK/QQ/JJ/TT so he only 4bet/call with AA/KK. I can understand why he flats AK, but the EV he is losing out on preflop has to be transferred to boards where weak players can't fold their 2nd pairs in 3bet pots and go all the way with it (like QQ on A/K high boards) to justify not 4betting it preflop.

HodorIsKing

Flatting AK vs most positions beein IP should be a good exploit vs a pool that could be 3betting not enough.
But there is also a good theoretical reason to flat AK more often esp. vs BB.
In theory the BB gets 3bet more polar vs all positions and the correct answer vs this strategy is to 4bet more polar.
In this scenario AK becomes more of a call because BB will jam or fold more often vs your 4bet and AK has no incentive for this.