A Chain of Wars
Fernando Po was uncolonized, but Portugal had nabbed Sao Tome. I planted a colony nearby in Gabon, fabricated, and put troops on the isle. Portugal tried to respond immediately, but I had a few heavies nearby and sank their fleet. They didn't try anything further.
Of course they were allied with Castile, and the local AI thought this meant it would be a swell time to declare war on me and/or my allies (as though I was actually fighting Iberians; Castile was embroiled in the League Wars). Bengal was first, with its ally Yarkand. We outnumbered them, but my tech was still behind, so it was a very bloody war that drained most of my manpower. Before that completed, Chagatai launched an assault on my ally Tibet, bringing in a powerful Jaunpur. I had three active wars, and Ming loomed.
I managed to peace out Portugal for Sao Tome, first by getting a white peace from Castile. From Bengal I just took a couple hundred ducats; we had not managed to take any of its forts, and it didn't seem worth the effort at this stage to try to cripple them. I wanted to Westernize quickly. That left just the war with Chagatai and Jaunpur, which I honestly couldn't have cared much less about. I had been hoping to ally Jaunpur to wield against Bengal after all. I fought one battle for Tibet, but I didn't have the manpower or the will to keep throwing troops at them when they reinforced and returned. I withdrew, leaving Tibet to lose a chunk of land to the nomads.
Modernization
After that began the Westernization. It was painful as usual; when the treaty with Bengal ended, they attacked my longtime ally Ava, and I had to dishonor the call. The rebel-stomping and bottomed-out values for legitimacy, traditions, etc left me in no condition to help against Bengal again.
It is now 1588 and Westernization is complete. My legitimacy is in the tank, but my manpower has recovered, and I still have a bunch of ducats in the bank. I did manage to conquer half of Khmer during this period, and I colonized a bunch, including a decent chunk of Malacca and most of South Africa. I also had a 0/0/1 heir die of illness, and the follow-up 2/5/1 heir also died of illness at age 1; I'm currently without an heir, though my 4/1/0 ruler is still fairly young.
I'll be catching up in tech probably through 1625 or so, avoiding most offensive wars (I'll probably finish off Khmer but leave the rest). Westernizing eliminated my entire rivals list; literally the only nation I now qualify to rival is France, oddly. Hopefully this will keep Ming at bay while I finish catching up (and if they try to Westernize they'll probably collapse).
Looking Ahead With Common Sense Features
Once I'm done Westernizing I can pretty much do whatever I like. Typical late-game conquer sprees isn't an option unless I stack Discipline bonuses to counter the penalty that such actions will force on me (as I'll always be at -100 Karma with that playstyle). Now that I've Westernized I can no longer vassalize / diplo-annex any nations in my vicinity; I'd have to travel all the way over to Muslim tech lands to be able to do this.
However, Common Sense allows you to seize territory from a Protectorate at a small temporary penalty to liberty desire. So basically, what I need to do is use force release, core return, and focused conquering to weaken my strong neighbors, Protectorate everything I can (this does not take up a diplo slot!), then seize territory constantly. This should allow me to expand at a healthy rate without tanking my Karma, but it's going to require a whole lot more work than anything I've ever tried in EU before.
Influence won't help much with this method since it doesn't involve annexation and I don't need the relations bonus. Perhaps Humanist is the way to go here? I'm guessing seized territory doesn't come along in a docile state like diplo-annexed territory, but I've never tried. Religious isn't really necessary because I already have good local CBs from Expansion (and I can go into the Andes shortly with Exploration's CBs), though if I want to force-convert everything to Buddhist I'll probably need it. If only the Devoutness idea had a Buddhism-related bonus; something like a monthly +1/-1 Karma modifier (whichever direction takes you closer to 0).
I have plenty of time to figure it out, though, since I have a lot of teching to do before I can bother with ideas (and my next idea group will be military anyway). I'll see how the Protectorate thing functions first-hand and figure out what I need most. Maybe I can do this with Khmer to save on Admin points while I regain tech.