We can classify several quite different calculi for automated reasoning in first-order logic as instantiation-based methods (IMs). Broadly speaking, unlike in traditional calculi such as resolution where the first-order satisfiability problem is tackled by deriving logical conclusions, IMs attempt to reduce the first-order satisfiability problem to propositional satisfiability by intelligently instantiating clauses. The Inst-Gen-Eq method is an instantiation-based calculus which is complete for first-order clause logic modulo equality. Its distinctive feature is that it combines first-order reasoning with efficient ground satisfiability checking, which is delegated in a modular way to any state-of-the-art ground solver for satisfiability modulo theories (SMT). The first-order reasoning modulo equality employs a superposition-style calculus which generates the instances needed by the ground solver to refine a model of a ground abstraction or to witness unsatisfiability. The thesis addresses the main issue in the Inst-Gen-Eq method, namely efficient extraction of instances, while providing powerful redundancy elimination techniques. To that end we introduce a novel labelled unit superposition calculus with sets, AND/OR trees and ordered binary decision diagrams (OBDDs) as labels. The different label structures permit redundancy elimination each to a different extent. We prove completeness of redundancy elimination from labels and further integrate simplification inferences based on term rewriting. All presented approaches, in particular the three labelled calculi are implemented in the iProver-Eq system and evaluated on standard benchmark problems.