Think of the circuit protection as creating a safe perimeter. Everything inside the perimeter can assume that there's no bad spikes coming down the line. You just have to apply protection strategies to every wire that crosses that perimeter.
Usually that's pretty clear from the layout of your box. All wires coming into your box from outside are suspect. Some idiot (usually you the designer) is going to hook this up backwards or drag a live wire across the pins of the connector at some stage in the future.
Every wire entering or leaving the box needs to have protection near where it enters the box. Don't collect all of the protection diodes into a group on the far side of the circuit board. Those traces passing under sensitive components can zap them before the protection circuit can clamp the spike. Put the protection circuits between the socket and the rest of your circuit, to make a protected perimeter.
TVS diodes are very high-level magic. They can withstand big voltage zaps. You don't always need to have one TVS per wire. Look at the internal circuitry of the TPD2E001. That protects two data lines and a power wire with only one TVS diode.
But a TVS cannot protect against everything. If you hook up 12V to the TPD2E001 then it will explode and release the magic smoke. The sustained power dissipation of that kind of hard fault will overheat the TVS. So you need to add more components, such as a fuse. You will end up with layers of protection to cover each different type of fault.