Karl and Susan have agreed to come to our party, _______ has made Maria very happy.  that  which  who  what

To fill in the blank in the sentence appropriately, we need to choose a relative pronoun that correctly connects the clause to the main sentence. The options available are "that," "which," "who," and "what."

Here's the analysis for each option:

1. That: This is a restrictive relative pronoun, suitable for defining or identifying a noun. It can be used in informal contexts.
2. Which: This is often used in non-restrictive clauses and provides additional information that isn't essential to the meaning of the sentence. It usually follows a comma.
3. Who: This is used for people and is appropriate here since it refers to Karl and Susan.
4. What: This is generally used for questions or exclamatory statements and does not fit in this context.

Given that we are referring to the subject (Karl and Susan) and how their agreement affects Maria's happiness, the best fit here is "who." The correct sentence would be:

"Karl and Susan have agreed to come to our party, who has made Maria very happy."

Therefore, the final answer is: who.