The choice between using two M.2 NVMe slots or one large disk depends on your needs. If you need more storage space, two disks can be a good option, allowing you to separate systems and data. However, for optimal performance, one large disk may be preferable, as today's larger NVMe disks often handle workloads better. Also, if your motherboard supports RAID, you can configure it to increase speed (RAID 0) or reliability (RAID 1). Cooling is important to consider, as two disks can get hot, requiring good airflow in the enclosure.