Like any aspect of quality, system security is not bolted-on, it is built-in. What does it mean to build security into a system? Think people, processes and technology - in that very order.
Find the right people to envision, design, implement, deploy, operate, evolve, maintain and decommission your system. Equip them properly. make sure they remain committed to upholding security.
Let these very people create, execute and maintain robust usable processes for the system life-cycle.
The rest is technology.