I will be installing 3 exterior flood lights ( each light has 3 - 150 watt bulbs). They will be controlled from 4 switches ( two 3 ways at each end, and two 4 ways in the middle). The last 4- way switch will go to a junction box that then feeds all three lights.

Wire run lengths are:
Panel to switch A = 19'
Switch A to Switch B = 10'
Switch B to Switch C = 49'
Switch C to Switch D = 15'
Switch D to Junction Box = 5'

Junction Box to Light 1 = 26'
Junction Box to Light 2 = 53'
Junction Box to Light 3 = 63'

I was planning on a 15 amp breaker and using 12-2 from panel to the switch, and 12-2 from the Junction Box to each light, the rest would be 14-3. My goal is to have as low of a load on the circuit as possible. Any recommendations ? Thank you.

Three 150 watt equals 450 wats equals 3.75 amps. You can use 15 amp breaker and circuit or 20 amp breaker and circuit. Wouldn't recommend mixing wire sizes. Later on someone sees 12 gauge wire and assumes a 20 amp circuit.

Use the longest run possible to have the Most resistance to have the load a low a possible with 3 150's.
To have the Maximum wattage(least resistance), it could be on 1 switch, fed from the Panel then X 10 3 ways at the other 3 locations.
Ideally, you want power to 1 3 way switch, then 2 conductors to first 4 way, 2 more on to the next 4 way, then to the last 3 way which should go to the lights.
Your layout may not allow that requiring you to pull additional conductors between boxes.

Use the longest run possible to have the Most resistance to have the load a low a possible with 3 150's.
To have the Maximum wattage(least resistance), it could be on 1 switch, fed from the Panel then X 10 3 ways at the other 3 locations.
Ideally, you want power to 1 3 way switch, then 2 conductors to first 4 way, 2 more on to the next 4 way, then to the last 3 way which should go to the lights.
Your layout may not allow that requiring you to pull additional conductors between boxes.

Thank you for your reply, but I am a little confused by your second sentence.
What gauge wire would you recommend? Is the idea of using 12-2 from the panel to the first switch and 12-2 from the junction box to each light, with the rest being 14-3 a good idea?

If just these lights, 14 would be fine. All wire should be all #14 or all # 12.

If just these lights, 14 would be fine. All wire should be all #14 or all # 12.

Thanks again. I will run 14-3 from the panel through the entire circuit.

Good deal. If you were having a receptacle on with these lights and it is in an area you might use a floor heater, then #12 and 20 Amps.
You're good though.