We will be flying into Madrid, going south and then back up to Barcelona. We will need to get back to Madrid for our flight home. Would it be wise to depend on an early morning flight on say, Spanair, to get us to Madrid for our 10:45am flt? Do all flights leave from Barajas airport and how long would I need between flights (on Spanair and NWA)? Or would it be safer to take a train the day before and stay the night in Madrid? Thanks for any and all suggestions.

For a 10:45 departure you should be in line at NWA's Barajas check-in desk by 8:45. Yes, all flights arrive & depart Barajas airport. You would have to be on a 6 or 6:30 AM flight out of Barcelona to cut yourself any 'slack' at all. No, it would not be wise to depend on an early morning flight from Barcelona. If you fly in from Barcelona your flight will probably arrive at Terminal 2 or 3; your Detroit-bound flight will depart from the new International Terminal (at the other end of the airport).

As for time between Spanair arrival and Northwest Airlines departure, it's not relevant: With increased security, your bags will have to be re-checked at Northwest Airlines check-in.

If it were me, I would spend the night in Madrid (probably at an hotel that provides free airport shuttle service).

You don't have to take a train the day before; there are three airlines servicing the Barcelona-Madrid 'corridor' with hourly service.
P.S.
Several years ago I went thru Barajas the morning an Air Traffic Controllers' Strike was beginning. That was Ugly!

Thanks so much for the valuable information. I guess we'll plan on leaving Barcelona a day early.
Any suggestions for a hotel in Madrid which would be easily accessible to/from the airport?