In lane, punish the last-hit itself: throw split Qs from side angles that make the dodge unclear, and thread W through the minion line so one cast farms and chips at the same time.
Vel'Koz damage usually starts one spell before R, so treat the laser as the receipt for chip, E, allied CC, or a burned dash rather than a neutral opener that has to do everything by itself.
Vel'Koz feels best when the map compresses into shared space—short side-wave catches are fine, but extended side-lane time makes his range fake, while recent data says longer grouped games still give him room to recover after a rough lane.
Against a target with options removed, not just health missing. In practice that means you have already tagged them with earlier damage, they are slowed or knocked up, they just used the dash that would leave the beam, or a teammate has pinned them long enough for you to hold the channel. If none of that is true, keep playing the first part of the fight with Q and W and wait for the step that becomes predictable. You will get more good ult casts by being late than by being early. The cleanest Vel'Koz lasers usually feel boring right before they become lethal.
Vel'Koz's abilities apply Organic Deconstruction to enemies on hit. If 3 stacks are accumulated, the enemy will take a burst of true damage.
Vel'Koz shoots a bolt of plasma that splits in two on reactivation or upon hitting an enemy. The bolt slows and damages on hit.
Vel'Koz opens a rift to the void that deals an initial burst of damage, then explodes for a second burst of damage after a delay.
Vel'Koz causes an area to explode, knocking up enemies, and knocking close enemies slightly away.
Vel'Koz unleashes a channelled beam that follows the cursor for 2.5 seconds that deals magic damage. Organic Deconstruction Researches enemy champions causing them to take true damage instead.