Has anyone taken a flight from Madrid to Lisbon? We are thinking of flying from Madrid to Lisbon, and stay 3 nights in Lisbon. My dilemma is whether to fly back to Madrid and then fly back to the states or fly to the states out of Lisbon. Madrid is much cheaper and has better flights.
Any thoughts?

when is this? Maybe we can expect travel restrictions or complications made if this is during late fall and over winter.
to price up just how much cheaper it is then you have to take into account all expenses. public transport or taxis to and from the hotel and airport for each change. loosing a day or more by traveling back to Madrid.
There could be other factors but you have not laid out the itinerary. That could also affect what we say in answer.

This is for late April 2023. Good point about the taxis and public transport.

Keep in mind that three nights is only 2 full days. Fares and flight schedules will likely change between now and April 2023, and the ideal flight times might disappear in the end, even if you commit and buy tickets now. You'd have to anticipate the possibility of a delay/cancellation when you pick a return flight to Madrid and build in some extra time, preferably arriving Madrid the day before your flight home.