Why is it that drugs are good/okay in Vice City, but bad in III and San Andreas?
Rockstar really seems to like to zigzag back and forth in regards to their GTA protagonists' support or opposition to the use of illegal drugs. They are most certainly your enemy in GTA III and San Andreas, yet everybody uses them in Vice City and you don't really have a problem with them. Then you have IV where they are vilified and made immoral again, but Chinatown Wars shortly afterward had you even selling them openly on the streets.
I don't know what the deal is with them in LCS, VCS, and V, but I can't imagine that it's very consistent there either. What's the reason for Rockstar continually jumping back and forth? They can't be too worried about offending anybody, because anybody who could be offended by these games most likely already has been offended by them.
It probably depends on the relationship between the protagonist and the drugs.
In GTA3, the drugs weren't villified so much as they happened to be the domain of your enemies. The Colombians were too entrenched in the drug market to possibly try and compete, so Claude and his allies just did what they could to destroy the drug market.
In VC, it was the 80s, and Miami. Drugs flowed as freely as the neon lighting up the streets. Not to mention, most of the clients were probably wealthier people, or those of backgrounds different from Tommy's (the Cubans and Haitians).
SA showcased the 'hood, and as CJ grew up in the 'hood, he saw firsthand the devastation drugs brought to his friends and neighbors. He hated drugs for that reason, and never seemed too keen on the heavier drug use by hisc friends (such as Ryder), and definitely not in the manufacture and sale of the stronger drugs like crack (despite being more tolerant of marijuana).
I don't know that IV villified drugs, either. It wasn't really Niko's forte, and while he might've disapproved of them, he also did do work with stealing drugs (especially that one cursed heroin shipment). Similarly, Johnny and the Lost dealt in drugs, even though Johnny found them distasteful, and Luis and his friends ended up being outright drug dealers, so I don't think IV was as anti-drug as you seem to think.
As for LCS/VCS/V, they didn't play a big role in LCS from what I remember, but VCS had a weird relationship. Vic (the protagonist) hated them because of what they did to his mother, but he ended up usurping a major drug racket in town and running his own drug empire up until the end of the game when he supposedly abandoned it. This was more out of necessity to survive, though, and he was never particularly happy he ended up dealing in drugs.
V is pretty lax towards drugs. They definitely aren't vilified, and one of the main characters is an active user of meth, who also owns a meth lab and supplies his close friends and the county he lives in with the product. All three characters have used marijuana, too, and can even do so during the gameplay if you choose. The story deals more with government intrigue, though, so drugs aren't exactly a highlight, Trevor (the meth guy) aside.
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I think Niko was largely indifferent to drugs. He only did deals or attacked other dealers at the behest of Jacob. And Johnny
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VC is based (in part) to the 80's Scarface remake film. VCS is VC's prequel story. So there's your answer.