Progress in developing analog quantum simulation platforms is reflected in increasing control of engineered many-body Hamiltonians, and the ability to perform single-site and single-shot readouts. This defines a new generation of programmable quantum simulators which combine a certain amount of programmability with scalability to large particle numbers. The focus of this talk is to report work from a theory-experiment collaboration with trapped ion platforms with up to fifty qubits/spins, with the goal to develop and demonstrate quantum protocols, addressing questions from the fundamental to the practical. Examples to be discussed include measurement protocols revealing the entanglement structure of the many-body wavefunction, and implementing `optimal' quantum metrology with variational quantum circuits, where quantum simulators act as `programmable quantum sensors'.