I dig GTAV too, but I think they will need to improve the interactivity of the game world in 6. Don't get me wrong, there's shitloads to do and miles to explore, but the ultimate GTA will have to take the best elements from V and meld them with the best elements of IV - more unrestricted access to building interiors (not just pretty locked facades, but places everywhere you can enter/break into; business, residential, recreational... a truly 'open' world), more complex and appropriate interactions with randoms (with different personality types responding to you differently), and just generally more life going on around you regardless of what you do, but that you can cause havok with and gain a noticeable street reputation (becoming a local 'character', like a popular rogue that many insignificant NPCs recognise and amicably holler at/show respect, or an anti-social brute/nutjob that people are wary of and leave well alone).
The next one should look to expand upon the openness of the world rather than simply the size, and increase the player's effect on the everyday running and minutiae of said world. Add that to a cool engrossing story and likeable colourful central characters, and you'll probably end up with one of the greatest videogames in history.
