The main objective of this research is to examine the performance, power noise, and thermal trade-offs in modern traditional (2D) and three-dimensionally-integrated (3D) architectures and to present design automation tools and physical design methodologies that enable higher reliability while maintaining microarchitectural performance for these systems. Five main research topics that support this goal are included. The first topic focuses on thermal reliability. The second, third, and fourth, topics examine power-supply noise. The final topic presents a set of physical design and analysis methodologies used to produce a 3D design that was sent for fabrication in March of 2010. The first section of this dissertation details a microarchitectural floorplanning algorithm that enables the user to choose and adjust the trade-off between microarchitectural performance and general operating temperature in both 2D and 3D systems, which is a major determinant of overall reliability and chip lifetime. Simulation results demonstrate that the algorithm performs as expected and successfully provides the user with the desired trade-off. The first section also presents a thermal-aware microarchitectural floorplanning algorithm designed to help reduce the operating temperature of the cores in the unique environment present within multi-core processors. Heat-coupling between neighboring cores is considered during the optimization process to provide floorplans that result in lower maximum temperature. The second section explores power-supply noise in processors caused by fine-grained clock-gating and describes a floorplanning algorithm created to work with an active noise-canceling clock-gating controller. Simulation results show that combining these two techniques results in lower power-supply noise with minimal processor performance impact. The third section turns to future 3D systems with a large number of stacked active layers (many-tier systems) and examines power-supply delivery challenges in these systems. Parasitic resistance, capacitance, and inductance are calculated for the 3D vias, and the results of scaling various parameters in the power-supply-network design are presented. Several techniques for reducing power-supply-network noise in these many-tier systems are explored. The fourth section describes a layout-level analysis of a novel power distribution through-silicon-via topology and it's effect on IR-drop and dynamic noise. Simulations show that both types of power-supply noise can be reduced by more than 20\% in systems with non-uniform per-tier power dissipation when using the proposed topology. The final section explains the physical design and analysis techniques used to produce the layouts for 3D-MAPS, a 64-core 3D-stacked memory-on-processor system targeted at demonstration of large memory bandwidth using 3D connections. The 3D-aware physical design flow utilizing non-3D-aware commercial tools is detailed, along with the techniques and add-ons that were developed to enable this process.