The design of cost-effective power systems with high shares of variable renewable energy (VRE) technologies requires a modelling approach that simultaneously represents the whole energy system combined with the spatiotemporal and inter-annual variability of VRE. Here, we soft-link a long-term energy system model, which explores new energy system configurations from years to decades, with a high spatial and temporal resolution power system model that captures VRE variability from hours to years. Applying this methodology to Great Britain for 2050, we find that VRE-focused power system design is highly sensitive to the inter-annual variability of weather and that planning based on a single year can lead to operational inadequacy and failure to meet long-term decarbonization objectives. However, some insights do emerge that are relatively stable to weather-year. Reinforcement of the transmission system consistently leads to a decrease in system costs while electricity storage and flexible generation, needed to integrate VRE into the system, are generally deployed close to demand centres.