Energy conservation is a critical problem in wireless sensor networks (WSNs). Cross-layer design can provide energy efficiency through joint energy management and optimization. In this paper, based on two orthogonal modulation schemes- frequency shift keying (FSK) and pulse position modulation (PPM), we put forward a multi-layer energy efficiency optimal joint design approach for WSNs. Considering one of main parameters of modulation - constellation size as global variable, the design unifies the energy-efficient factors in hardware layer, link layer, MAC layer and routing layer, which accordingly include battery discharge nonlinearity, node circuit multi-mode operation, signal low-power transmit, a variable-length TDMA scheme and multi/single-hop routing. The total energy consumption across the layers and its minimization problem are hence formulated. Then, a string-star hybrid network derived from controlled deployments is taken as an example to numerically analyze and optimize the design. The results show that PPM-based design is more energy-efficient than FSK-based design in all our observed deployment scenarios. The energy-saving can be up to 75% for PPM-based design and 51% for FSK-based design, respectively.