Did you check your tie rod ends and king pins while you were under there. That would be my next place, check all the steering linkage while you are at it. Brakes are also an issue, especially if the knock is rhythmic like you described. Rhythmic knocking is usually something that rotates, or that can interfere with rotation, Like a piece of of something in the path, body panel, debris etc

Could be a lot of things: Tire out of balance, bent wheel, weak shock, loose steering linkage, alignment - You'll have to let a pro put it up on a lift & look around...

You have a bad U-joint in the drive shaft.

Its a ford.. Not suprised

I have a 2000 Ford E-150 with 178k miles. I'm the second owner and have always done regular maintenance. It vibrates when driving over 20mph. I feel it mainly in the front end and I occasionally hear a knocking sound coming from the undercarriage (at least one knock every 30 seconds). I've changed the wheel bearings and have balanced/rotated the tires. They have plenty of tread left (bought em last fall) and there's no sign of uneven wear. I like to do things myself, but I'd like to know what my next step should be? What would be the causes of vibration over 20mph?