Honestly, I don't think that there is anywhere that they could go with the series. TPP is set in 1984, so we're getting closer and closer to the original MG, which is set in 1995. The only real options would be to go for a pre-SE or post-GOTP world.
There's loads they could do, this is a Japanese IP after all. And even though I was joking and Kojima
does say it's his last Metal Gear in the leaked IGN video, I think it's a mistranslation - he says the Metal Gear
Solid arc is closed by TPP, so although the voiceover guy says it's Kojima's last Metal Gear game, I think Kojima means it's the last Metal Gear Solid game.
Personally, and I say this at every opportunity, I want to see a Metal Gear game where you play as The Boss in WWII because I think that, done right, could be absolutely amazing. The thing is, though, the Metal Gear timeline goes right back to 1860 when The End was born so it could easily become an Assassin's Creed kind of thing where each game goes to a different period in time and dresses up a villainous faction (like, say, the British side in the War of Independence or the Nazis in WWII) as being guided by - or just being - a precursor to The Philosophers, just as how Assassin's Creed explains a lot of conflicts as being the Templars doing... Templar things.
And The Twin Snakes was absolute rubbish (in my opinion, though I am pushing to have my opinions upgraded to universal truths), Metal Gear Solid's level design just didn't account for first person aiming, the M9 or PSG-1T so it was just trivially easy, or if I were to be more kind I guess I'd say the challenge of the original was completely changed into a different game. And that's ignoring the over the top (putting it mildly) cutscene direction that doesn't fit in with any other Metal Gear game except Rising.
The original is still a great game, it has aged far better than MGS2 has because the controls are simpler and the art style suits the limited graphical capability perfectly so it never looks like they over-reached what was possible at the time. The only actual problem with it is that you can't play it on anything but a PS1, 2 or 3. I suppose it's pretty simple to emulate, though, but I don't know how easy it is to deal with swapping the discs over. Point is, if it's not remade or re-released at some point, it'll die. Then again until they're all released on PC or game streaming becomes a thing, they'll die anyway.