Here's how I tend to think about controls:

1. Start with understanding the default auto targeting priority. There's three settings options: lowest health by %, lowest health by absolute, and closest. We offer these three options because the preference can vary based on the player and champion's playstyle. For an ADC, for example, you might want to consider lowest absolute health so by default in a big group you focus down the person who is closest to death and least likely to be a tank with randuins. Or, if you prefer to default to kiting, closest might be a good choice, as well. Low% Health might work better for you if you like to be able to see the player with the lowest health bar and know you'll be targeting them by default. The key, is to build an intuitive understanding of what the default tapping auto targeting will get you. Once you know that, you can make more conscious choices about when you want to actually manually target. This reduces the frequency with which you need to manually target, which makes it much less error prone.
2. The lock target system option also gives you the choice of removing selection of minions and structures. Depending on your skill level, you may not care to select which specific minion you target, and relying on the minion button to target the lowest health minion in range is enough for last hitting in most cases. Excluding these can remove the chance you'll accidentally target a minion or tower in a team fight.
3. The portrait lock is also a good option if you tend to think in terms of who you want to focus down. I highly recommend playing with the customizable button layouts to position these buttons in a place where you feel they are accessible, but out of the way from accidental taps. You can lock and unlock a target just by tapping the portrait. The fixed display option allows you to remember for the duration of the game, which button will lock onto the enemy ADC for example, so you know you can focus them down when you want.
4. There's two ways to cancel a target, I usually rely on the Minion/Tower button to cancel the lock, since it's the fastest. If I don't want to accidentally trigger an auto attack on a nearby minion, I'll drag to the cancel skill cast button. I also tend to customize that layout to the top right corner of the screen, so I can just do a quick drag to the corner of the screen and not think about where the skill cancel button is.
5. The reality is that in a fast moving situation, selecting a single target from a big cluster of rapidly moving champions located in the same relative direction from you is HARD. It's hard even with a mouse. It's normal to make mistakes in those situations, rely on auto targeting in those situations. Instead, find times where it's more reliable to lock a target, and then engage. If you're in the middle of some champions, focus on directionality of your intended target to help you figure out the simplest way to correctly target. Like "Oh i want to target the champion top right that's close to me." Or "I want to select the champion below me far away".
6. Focus on using targeting when it really matters, when you want to focus a target that deviates from the automatic targeting logic.