The guest lecture by Reynold Xin at Stanford University discusses Spark and its advantages over MapReduce, emphasizing the simplicity of programming and performance benefits for large datasets. It introduces the concept of Resilient Distributed Datasets (RDDs) as a core abstraction in Spark, highlighting their fault-tolerance and parallel processing capabilities. The lecture also covers Spark's application in streaming, machine learning, and SQL, showcasing its versatility in data processing tasks.