This paper proposes a system-aware, fully programmatic and automated, process agnostic design methodology, which utilizes system-level simulations with the layout parasitics of the circuit under optimization included. The methodology is demonstrated with a design procedure for a comparator from specification to layout implementation in three analog-to-digital converter design examples with different specifications and applications without designer interaction. The procedure is shown to effectively converge towards performance achieved with ideal comparator in post-layout across two different semiconductor processes. While the methodology was demonstrated for design of comparators, the proposed system-aware methodology is generally applicable to any analog circuit, drastically reducing design time while providing a silicon ready circuit implementation purpose designed to the higher level system without human-in-the-loop.