Quantum simulation aims at `solving´ complex quantum many-body problems efficiently and with controlled errors on quantum devices. Here we discuss quantum simulation from the perspective of programmable analog quantum simulators, as realized in present cold atom and ion experiments, where the unique features are scalability to large particle numbers and programmability. The focus of this talk is to report work from a theory-experiment collaboration with a programmable trapped ion platform with up to fifty qubits/spins, with the goal to develop and demonstrate a toolbox of quantum protocols, addressing questions from fundamental quantum science to application as quantum technology. Examples include variational quantum algorithms preparing many-body ground states, and measurement protocols revealing the entanglement structure of the many-body wavefunction, e.g. as tomography of the entanglement Hamiltonian. In addition, we demonstrate `optimal' quantum metrology with variational quantum circuits, where quantum simulators act as `programmable quantum sensors'. Finally, we address the problem of verification of quantum simulators via Hamiltonian and Liouvillian learning as an experimental protocol, i.e. we `learn' the operator structure of both the many-body Hamiltonian and Lindbladian characterizing (Markovian) decoherence.