How realistic is whole-home Thunderbolt for lighting and smaller appliances?

Whole-house 12/24VDC power wiring has been a thing for at least 50 years, specifically intended for lighting. It's never proven widely popular, but it's certainly a realistic option. Probably more so in new construction than retrofitting into existing buildings, though.

Whole-home PoE for lighting might be another interesting approach!

In either case, you'd need a very beefy DC power supply somewhere to get enough current, or individual power supplies scattered inside walls, etc. which sounds like a maintenance nightmare.

Or keep the voltage high and step down with a buck converter in each socket as needed and negotiated with the device: there's a good argument to use ~300VDC as a future home electrics design. High-power devices (water heaters etc) will work better and more efficiently with DC, and low-power devices can deal with 48VDC with a lightweight step-down converter (5A buck converters are tiny)

From a purely technical standpoint, I agree completely. However, given the debacle around USB-C cables & PD, I'd be very worried about a world where I have to trust devices to properly handle such high voltages.

How safe is working with 300VDC?

Half-way there to 600 VDC traction power!

The LED strip behind my TV is powered by the USB port on my TV. Most longer strips (5m-20m) use one of a small number of form factor strips and 12V or 24V supply. There are also quite a few USB powered lamps, but a bulb form factor would be interesting.