Great idea for a thread.
1. iWork (The REAL Version)
(Make it a complete and robust office suite. Apple is on the right track here, but they should be thinking of it as a competitor to Office, not a replacement for Appleworks.)
2. Photoshop killer.
Adobe's app is too complex, ugly and slow
3. Update FileMaker's UI.
It actually is a great DB program, but the UI sucks. And the fact that it is cross-platform is not a valid excuse. itunes is cross platform, and nothing in Windows limits FileMaker from doing better.
4. A robust PIM.
Doesn't need to be 1 app, but iCal and AddressBook are terrible and way out of date.