The Las Plagas gave Saddler and eventually Irving, Excella and Wesker total control of creatures implanted with the parasite. Those infected by the T and G-Viruses acted on complete instinct and could not be controlled. T-Veronica was proven to be unstable if not dormant for 15 years. Uroborous is most volatile if the DNA is rejected.

Whether creatures can be controlled or not are both quite dangerous either way. However, the creatures that act on instinct are more unpredictable where even the villains have to defend themselves or be forced to contain the creatures. How should the next batch of creatures be handled?

Both. Have one type or group of enemies be controlled (Las Plagas, or an advanced strain) and other group infected with the T-G, etc. viruses. It'd add variety to the game and to the strategy on how to defeat them, especially if there's a room with both types attacking you (since like you say those infected with the viruses are less predictable in their attacks).

I think they should act on instinct, that seems to have been how they always acted in the past games.

Act on instinct. Makes them more sinister. If I am correct, the Regenerators were on complete control of themselves, which is why I think they were more terrifying. Nemesis is yet another example.