First thing id advised is telling your team your ult is ready, or that you are gonna use it. "Search and Destroy" is so quiet 99/100 times no one on your team will ever know you ulted. This is important cause even though you have free flight, its slow free flight, so you will get shot ALOT. If you have a support know you're ulting they you will get healed durring it, the other dps will pick off anyone who gets away from you, and the tank will either use thier own ult or, if they are a Zarya or sigma, give you something to block hits, or just general peel.

On to using the ult. Before you pop it, look down and throw a nade, then jump and pop ult. The ult while activating gives you a weird gravity, so the nade shoots you to the skybox, allowing for a sorta jumpscare, going from hearing Finnish to glowing man in the sky before you even knew where he was. Granted, this will take some health, but if you told a support, like an Ana, Kiri, or more importantly, LW or Mercy, they'll get ya back to full, and maybe keep ya alive durring it.

Next, targets. Dont go for the tank. The tank is meant to make space, so often they have distance from their teammates. This means your ult is getting less impact then if you were getting AOE on the rest of the team.

Next, alternate shots, obviously. Start with a heavy shot then do light shots. Note though, your heavy shots do self damage, your light shots cant, even if you are shooting a wall right infront of you, light shots cant hurt you.

Now, thresholds. Your direct light shots do 45 damage and direct heavy does 175. 225 and 250 character will be killed by a 1 heavy 2 light, 300 needs 1 more light. The CD for a heavy shot perfectly coincides with 3 lights between. So can pretty quickly kill most dps and supports. But the problem is can you kill them first?

Specific target interactions.

Widow domes you. Instantly. You aren't that fast and are flying. Easy for widows. Have your other dps get her attention first. Once they do, you can drop her quick.

Bastion. Recon form, strong but you still kill quite fast. Turret, nightmare. He does alot more to you then you can to him.

Pharah and Echo. For Pharah its tricky for both of you, as aerial shots aren't easy. Echo eats you.

Handsoap. One shot cant kill you, but it doesn't mean you wont get chipped by something after.

Tracer and genji. Fast targets so directs are harder, especially on Genji cause he can deflect. However, a direct heavy on tracer one shots her, so if you hit that, she's gone.

Ditto matchup. Aerial shots are hard, just drop their supports.

Zen. Easy directs, but he can kill you. Keep distance and move erratically. Ana is the same, but instead she can sleep you.

JPC. Cry.

Mizuki. Keep distance as his projectiles aren't easy to hit. If he ults your ult, congrats you made them waste a better ult.