Handgun with the simplest manual of arms:
Thompson Contender. Drop in a round, snap shut, pull trigger. FTF drill: try again.
Derringer. Drop in 2 rounds, snap shut, pull trigger twice. FTF drill: try again.
(Remember, you asked about handguns)
Then DA revolver. Drop in 6 rounds, snap shut, pull trigger 6 times. FTF drill: Pull trigger again.
Then single action revolver. Drop in 5 or 6 rounds, shut loading gate, cock hammer, pull trigger, repeat as needed. FTF drill: cock hammer and pull trigger again.
Then striker fired autos with no external safety. Shove in magazine. Pull back slide. Pull trigger until gun stops. FTF drill: Tap, rack, fire. If no bang then drop mag, rip slide several times, reinsert mag and then tap, rack, fire.
Then in descending order of simplicity: DA/SA or DAO autos, the single action autos, then black powder revolvers, then black powder single shot percussion pistols, then black powder flintlock pistols, and then it depends how far back in history you want to go.
Notice that simplicity has nothing to do with speed, capacity, accuracy, or size. Everything is a trade off. The perfect handgun would require no action from the user but pulling the trigger, and would have unlimited capacity, infinite power, infinite capacity, pinpoint accuracy at any distance, weigh nothing, fit everyone, and have no recoil, and be immune from negiligent discharge, and be one hundred percent reliable and only be operable by the user and not be a theft risk.
Let me know when they start selling one, I want to buy it.