Off the top of my head, I can list at least a score and more of actors from the four southern languages spanning over five decades. For the sake of contemporaneity, and leaving all lead actors like Kamal Hassan, Vikram, Mohanlal et al., I zero in on just one actor, who in my opinion is the very epitome of versatility.
Prakash Raj
Hailing from a rich stage background from the Kannada theater, this thespian has straddled the south Indian tinsel scene like a colossus in all the four languages(and also recently, Hindi) for nearly three decades, bagging along the way one National Award for Best Actor, one for the Best Supporting actor, one Special Jury awards, four Tamilnadu State Film awards,a handful of Filmfare (South) awards and half a dozen Nandi awards for his performances covering an entire range of roles. Here I will be talking only about his master class performances in Tamil films and some stray Telugu films, and leave the field open for my friends from other South Indian states to chip in with their contributions in the comments, or as separate answers.
Aasai (1995) : Perhaps in his first major running role, his performance as a cantankerous Army Major coveting his unwed sister in law, Prakash Raj oozed with a menacing meanness. In fact his performance as the scheming antagonist totally overshadowed the protagonist played by an young and handsome Ajith Kumar. In the same year he won his first Tamilnadu State Film award for best villain for his role as a sadistic husband in the movie Kalki directed by his mentor in Tamil, K.Balachander.
Iruvar (1997) : In this cult classic directed by the maestro Maniratnam, a thinly veiled political drama about the relationship between M.G.Ramachandran and M.Karunanidhi, Prakash Raj donned the complex role of Thamizhselvan modeled on Karunanidhi’s persona with great aplomb while pitted against another thespian Mohanlal in the role of Anandan closely resembling M.G.R. Prakash Raj won his first National award, for the best Supporting Actor for his excellent portrayal.
(Prakash Raj in Iruvar)
Antahpuram (Telugu-1998) : Prakash Raj played the elderly Narasimha, a violent and uncouth village chieftain with great authenticity,which fetched him another National Award (Special Jury) Prakash Raj also produced and reprised his role in the Tamil movie under the same name in 1999.
(Prakash Raj in Anthapuram)
Appu (2000 film) : In this movie Prakash Raj donned the role of Maharani, a transgender brothel keeper, reprising the role made iconic by Sadashiv Amrapurkar in the Hindi original Sadak, and delivered a power packed performance, as usual eclipsing the hero in every scene.
(Prakash Raj in Appu)
Okkadu (Telugu-2002) / Ghilli (Tamil-2004) : The negative role played by Prakash Raj in these Tamil/Telugu movies attained a sort of cult status, with his way of addressing the heroine as “Chellam” (Pet/Darling)became a trade mark of the actor.
( “Chellam” Prakash Raj in Ghilli)
Vasool Raja MBBS (Tamil-2004) In this Tamil remake of Munnabhai MBBS, Prakash Raj played the arrogant yet adorable Dr. Vishwanathan, matching the incomparable Kamal Haasan stride by stride in every scene they appeared together.
(Prakash Raj with Kamal in Vasool Raja M.B.B.S)
Anniyan (Tamil-2005) : In this movie as the cop in hot pursuit in the trail of the elusive Anniyan, Prakash Raj still managed to hold his own against a rampaging Vikram in an author backed role and won the Tamilnadu State Award for Best Villain (though I personally would not consider his role in the movie as villain)
(Prakash Raj with Vikram in Anniyan)
Bommarillu (Telugu-2006) / Santosh Subramaniam (Tamil -2008) : The role of Prakash Raj as an overbearing father dominating over every decision of his son was the pivot for the whole movie.
(Prakash Raj in Santosh Subramanian)
Mozhi (Tamil - 2007) : In my opinion, the best ever performance of Prakash Raj, in a parallel role as the fun loving friend of the protagonist, he could hold out against his much younger co-stars, and set the screen on fire with his spontaneous comic capers. Truly international level.
(Prakash Raj in Mozhi. Incidentally he was the produer too)
Arai En 305-il Kadavul : Prakash Raj played the god in this comedy, totally shedding his villain image with a very benign and calm look in his eyes.
Kanchivaram (Tamil-2008) : The crowning glory of an amazing career. Prakash Raj’s understated and poignant performance as a suffering silk weaver in the pre independence India, very deservedly fetched him the National Award and Filmfare award for the Best Actor.
(Prakash Raj in his award winning role in Tamil movie Kanchivaram)
Abhiyum Naanum (Tamil-2008) : In this home production of his, Prakash Raj turned from the hated villain of Trisha in Ghilli to her doting father, turning the dominant father of Santosh Subramanian into a caring and loving one for his daughter. This role merits a mention just prove how he could achieve such transformations effortlessly and with total ease.
(Prakash Raj with Trisha in Abhiyum Naanum)
As I said in the beginning, this list covers only Tamil movies, giving just a fractional glimpse of the versatility of Prakash Raj. If we take into consideration his performances in Telugu, Kannada, Malayalam and Hindi, we can realise the full extent of his enormous talent.
( All images are from the internet)