As someone who plays a lot of RPGs and who makes them too...
It depends.
First, It depends on the number of small guys, how hard they hit, and (if it's an action game), whether they can pincer you for the big one to get a free hit in (*extends middle finger to the Dark Souls 1 Capra Demon*). How fast can I kill them, etc.
Then, I have to consider the big ones. How painful are their hits? Can I debuff them or lock down their strong skills somehow?
Finally, I have to consider my own abilities. Do I have some AOE stuff I can use to hit them all? How many will it take to wipe the herd? That kind of thing.
So it fluctuates based on the encounter. In fact, in a game I made, I can cite two encounters in a dungeon that demand different approaches.
1) Scorpion with 2 bees. Here, it's better to hit the bees first. They go down relatively quick, and while the Scorpion has poison and (I think, it's been a while) a multihit attack, it's not THAT deadly (especially if you debuff his attack). Whereas the bees will prevent you from evading and are generally a big nuisance. Ergo, they go first.
2) Dire Wolf with a bee and an imp. Dire Wolf goes first. Always. He does good damage but isn't immediately a big threat. Then, on turn 3, he Hastes himself and gets TWO actions each turn as well as double normal attacks. This suddenly makes him a HUGE threat. Ergo, he goes down first.
In fact, that dungeon's boss plays off that idea too, making you switch mid-fight. It's a big beefy high attack plant with two mook plants next to it, one that heals and buffs, and the other that does all kinds of nasty status effects. Oh, and the big plant puts up vines that "Cover" the smaller ones and make their defense go up to impossible levels. Now, taking on the big guy is a terrible idea, as the buffs from the smaller blue plant will make him LETHAL. So the idea is to silence the smaller ones to stop the buffs/debuffs until the main character can use a skill to remove the "Cover" status from the smaller plants, and kill the buffy one. THEN, you need to switch and focus on the big one (using silence on it) to stop it from reviving the smaller one you just killed. Once the big one is dead, the fight is essentially over.
^_^ This was a fun discussion!