JavaScript and Chrome: Why does for...in run extremely fast the first time, but subsequent runs are slow?

TL;DR: It's a missing optimization in V8's optimizing compilers (Turbofan and Maglev). I've created a bug on the Chromium tracker, and I'll fix it in the next few days if I have enough time. (and also, your benchmark doesn't benchmark what you think it does, cf the latest section of this answer)

Technical details:

The missing optimization is that V8 doesn't constant-fold loads from the script context when compiling a closure whose code has been instantiated multiple times. Here is an example:

const o = { a : 42 };
function makeclosure() {
  return () => o.a;
}
let closure1 = makeclosure();
%PrepareFunctionForOptimization(closure1);
closure1();
//make_closure()(); //