One can simply cast their Ult before main engage occurs

This deals (Number of alive enemies) * ( Ult dmg ) = alotta dammage! Now compare this to cleanup with Requiem into 2x 300HP targets, after allied team is ded and unable to participate because of...lack of dmg earlier, ofc.

PITIFUL CAPITALIST WASTE!!!

Preemptive Ult guarantees free dmg , applies short duration effects like antiheal, burn for more dmg, slow from Rylai's Crystal Scepter or vision from Horizon Focus. Which enables allied follow-up. Slowed squishies with lost HP become easy targets for skillshot-reliant long ranged or mobile champs. Problem is: 1s slow duration. So, coordination is key if you want utilize those effects. But more often than not, damage alone is enough...Karthus also free to spam Qs after going into Death Defied wihout caring about unspent Ult .
*Do not cast ult too early ( like 5s+ before its dmg can be followed by allies) if enemy can heal up/shield everyone, and prepare their CDs for the next stuff.

Seriously, become free of this mental block preventing yall from preemptive ults.

When an opponent sees the zone from the Q ability appear beneath them, they try to escape it via the shortest path, which is Q radius. Otherwise they will be hit by it. By dropping non-centered Qs you can force them to move in desired direction .
With sequence of Q's thrown in such way, you lash them out of somewhere or create perimeter outlining their "cage" they are trapped in. This should be abused by your allies, or your movement closer (between the casts) until you can reach the enemy with ur Defile.

To gain some distance from the enemy, draw the line between you two, then drop ur Q on that line so they will be hit by its full size if they continue to chase u. Start moving away, along this line.

Similarly, you can prevent enemy from escaping Defile range by blocking their way with Q, by dropping it slightly beforehead, partially covering them ( by 1/2-2/3 of Q square)


You can try the following:

Drop Q under enemy center. They will move out along radius. Drop another( non-centered) Q beforehead, into that line asap. Such way that it mostly covers their hitbox, for like 2/3-3/4 . Idea is: More often than not people do not understand when they can turn back/ side to dodge next Q, and they have reaction time, and such slightly non-centered Q leads to confusion and misplay.
They will continue their jukes, until it fails and they r hit by slow from Rylai's Crystal Scepter , and Q'd to the deth.
If they try zigzagging instead of going straight line, drop second Q closer to the 1st. Zigzagin will play against them.

NOTE: THIS WORKS WITH HIGH CHANCE MOSTLY THANKS TO HUMAN REACTION TIME. If enemy has lightning reflexes or 400+ MS, or Q CD is more than 0,7s( 40 haste), this may be useless. With more haste you can make this trick more reliably, BUT:
Some players know that delay between Q cast and its actual dmg lies between 0.528 and 0.759 seconds, meaning THEY CAN SIMPLY STEP ASIDE ALMOST REGARDLESS OF YOUR ABLILITY HASTE.
Even in this case, you can still create a zoning "perimeter" for allies by casting non-centered Qs, forcing enemy to move out of them shortest way.

Should not be too difficult if you practice all this vs bots before going into PvP. Mechanics are very important on Karthus.

*Some Karthus' skins give advantage to enemy, providing more visible Q landing zone.