I don't fully understand yet why Vitest wouldn't load this through Vite module loader yet. If anything, this comment needs to be enhanced a bit to clarify this.
I also don't fully understand why this global is causing problems but the other globals in this file do not - would they also cause problems if we started using them for more than booleans, i.e. property access?

You're right. I was completely misunderstanding the issue. Vite does perform the global variable replacements. It's just that our globalThis.__sveltekit_dev object is undefined unless it's defined by our server rendered page.

So the only issue was accessing a property on an undefined object. I'll just add an optional chain.

Inside vite/index.js we have

// @ts-ignore this prevents a reference error if `client.js` is imported on the server
globalThis.__sveltekit_dev = {};

I wonder why that isn't working? Is it because for Vitest the if (build) branch is used? If so, should we instead add a "is this Vitest starting this build if so add the globalThis in here like we do in dev"? Or could this cause problems in other places?

Inside vite/index.js we have

// @ts-ignore this prevents a reference error if `client.js` is imported on the server
globalThis.__sveltekit_dev = {};

I wonder why that isn't working? Is it because for Vitest the if (build) branch is used?

Definitely not because of the if (build) branch. I can reproduce the issue here where the globalThis is not the same when logging it in the test file after running pnpm test: https://stackblitz.com/edit/vitejs-vite-tycr5kae
Maybe it's because test files are run in a different thread so they don't share the same globalThis? https://vitest.dev/guide/features.html#threads