For a new D&D campaign I'm planning, I would like to design a grand villainous plot
Ok. On some level that's easy. On another level, the one where you are trying to be original and bring the awesome sauce, that's hard.
For me I always try to begin with some broad exploration of themes. What is really going to be at stake during your campaign? Figure out the question, and make your villain(s) a particularly nasty answer to it.
So, for example, in my current campaign the overall plot began as a meditation on the following question: "In a massively polytheistic setting with hundreds or even thousands of gods, each deities beliefs are another deities heresies. It's obvious such a society would still have the notion of blasphemy, but since each society will worship multiple gods, will there still be anything like the notion of heresy on a socio-cultural scale? Or put it another way, if you had clerics of multiple deities in the room who each agreed that the other's teachings were blasphemous, would there be anything that they could all agree was heretical?"
My villains in the current campaign are the answer to the question, "What does a heretic look like when no one can agree on what is the morally correct way to live?" And what's at stake - at least at as I see it, since my players aren't yet engaging it at this level - is really the question, "Given the setting, would I also be a heretic?"
So, that's where I'd start. Obvious questions might be:
a) Do the ends justify the means? This one is always good, particularly because players tend to always think in terms of their ends justifying their means. Present a horrific problem which has as its most solution something absolutely appalling. The level you go for here to be pitched to just how stomach churning of a problem you think your table can handle maturely. The villains here might actually turn out to believe they have very good ends. Alternatively, the mentor faction the players are working for turn out to know why the villains are doing what they do, and not only don't intend to stop it, they intend to coopt the villains solution - disagreeing over neither the end nor the means, but simply who can most safely, humanely and effectively carry it out.
b) Who has the right to rule? This idea exploits politics by having some sort of succession crisis following a civil war, assassination or the like, and then puts the PC's in the position to choose sides where each side has some sympathetic claim to the throne - clear legal right, popular support, benevolence, nationalism, etc. For example, one claimant might turn out to be the real clear legal heir, but also be a bit of dimwitted fool or otherwise clearly unfit as a leader. Another claimant may have considerable popular support, but be a ruthless usurper whose claim to the throne is based on deceit. Another claimant might be neither popular nor the rightful heir, but instead be clearly the most likely to be a good ruler if he were to ever come into power. Another claimant might want revenge against the usurper, justly citing how the native ethnic population has been repressed and even at times genocidal cleansed since the land was conquered some time in the past, and will restore the land to its former racial purity, ejecting the conquerors and allowing once more the people to be ruled by one of their own blood. And so forth. This campaign depends on playing with the players perceptions, with each clamant being put into a bad or good light in turn as you appeal to ideas that are ideally unified - legitimacy, rule of law, mandate of the people, merit, etc. - but here are horribly fractured.
c) Rough men stand ready - A version of the do the ends justify the means. The PC's belong to an utterly benevolent society upholding every virtue. The only problem is that they are utterly unable to defend themselves against some existential threat to their existence because they are unwilling to embrace a laundry list of things that they find morally reprehensible - such as murdering innocent victims of some parasitical plague, committing genocide against another ethnic or racial group, using demons as oracles, practicing necromancy, or any number of similar things. If you want to go for a potentially less challenging level, maybe the society is simply pacifists. The PC's must become criminals within their own society. The real knife edge being, can you fight evil with evil without becoming the very thing you are fighting? Obvious plot twists can be, the final solution involves something that the PC's no longer are capable of doing because their too tainted, and some morally pure person must be convinced to make the final sacrifice - despite the fact they no longer have any reason to trust the PCs.
d) Nature vs. Technology: On the one side you have arcanists and engineers building a prosperous largely rational society, but who are ruthlessly exploiting resources - cutting down forests, polluting streams with sewage and mine waste, burning coal to heat their cities, and so forth. On the other side you have a bunch of animists and nature spirits, who want to be left alone or live in simple ancient ways - even if it means a hard rough life with an occasional human sacrifice on the side to keep the crops growing. Choose a side, or try to come up with a compromise. The DM should cleverly hide some of the consequences of choosing a side and prepare for paradigm shifts along the way. I'd play this as, ultimately, the leaders of both sides are very charismatic villains, however I can support the players political preconceptions to hide that fact - leading my greens or capitalists easily astray so that their prejudices blind them to what is really going on. Fully backing one or the other leads to horrific disaster, possibly realized to late to prevent it if they don't have their eyes open. The real solution might involve defeating both sides and finding leaders within both factions that are less ruthless and more charitable. For a group less in to moral dilemma and crisis, you could pick a side and play it straight.
e) Freedom vs. Security: Probably a variation on 'who should rule', you present two possible social orders - perhaps warring nations. One nations citizens have significant freedom and attendant prosperity, but consequently misuse it frequently leading to common social ills. The current rulers are a less than savory group of oligarchs who've held on to power for generations. Another nations citizens are completely secure, but only at the price of being effectively slaves. The current ruler is a benevolent philosopher king. Which ever side the players start with, initially sympathize with, pull the rug out from under them by having the society undergo a change of administration - the benevolent philosopher king is replaced by his insane psychopathic son and the people go right on faithfully serving him, the people peacefully overthrow the oligarchs in favor of a benevolent group of reformers, or conversely the oligarchs or replaced by the most ignorant sort of mob rule and would be dictators. Again, you can really screw with a groups political biases here if you wanted to, which throws on some level of ends versus means via ideological purity vs. practical outcome.