I think Spain should be very aggressive, some tips:
-Spain will never renounce to Italy. Italy, and its cots are more than a simple objective, it's Spain's everything. If Austria wants Italy, don't support the unthankful bastard
Italy represents MP, wealth, a strong base to rule in the mediterranean. Personally, I'd take Languedoc, Provence and Savoy later on to connect those lands.
-Spain should take Timbuktu before anyone and support Hungary as Austrian. Weakening the beast Oe is always a good thing to do because they can build sails like mad, or it can use its MP to crush Austria, your ally against France.
-Crush France early, a good player should take Mexico in 1495-96 or even earlier if there's luck with Columbus. After having Mexico, Spain's incomes grow to 110-120. mint, don't wait, France is a crt behind you
-In the beginning of the game, ally Naples, then Navarra.
-Ryo's right, before converting, make minimum fortifications in your colonies. Trade!!! no one's competing in the east, what are you waiting for? use explorers and Portugal! never let your explorers die of boredom, neither let your conquistadors stay in a province hunting flies. send them to the north, discover NA completely if you can, South America, the Cot in Delhi after Mughals relocalization of their capitol event, Malacca, China's Cot, Japan, Isfahan, Zanzibar, etc. Cots are important for you!
-Optional* a bad Oe player would wait till 1510 to annex Mameluks. after the french war, or after you get land 9, attack Mameluks, you have cassus belli! take Alexandria, sell it later, or keep it as yours. You can get a lot of money from Oe by doing this, or you just simply hurt Oe a lot!
-Optional* Netherlands is hard to protect, it's reformist and it causes great pain to your treasury to keep it without rebels. give it for money (never to France) release NL (bad idea in long term) convince Austria to keep it in exchange of Money, support, Italy. NL's not worth that much for Spain.
-Optional* (gamey too) give Portugal 3 secret american gold mines to avoid bankrups
-Optional* colonize in Asia, Africa or India. I always colonize Phillippines, it's a good base to conquer China's cots, Malacca (if there's no Portugal), then India why not? set a base in India, an island or something close to isfahan, you'd love to surprise OE there (Egypt, and Irak especially).
-Spain usually has inflation problems, annex and convert pagans, build colonies (never have 6 colonists!) use them! after explorations, use explorers, conquistadors to set colonies quicker and cheaper. Invest hard in Infra till infra 5, I use to have infra 5 in 1545 or 1550. after that you can invest in trade as much as you can.
-Some pagan provinces in America (especially Incas) can be converted spending 50 or 60 coins because those provinces may have less than 5k inhabitants around 1510. forget fortifications, place troops and convert them!
-Spain depends on sails to keep the empire safe, make galleys, more than Oe (always!) Then get infra 5, place governors in every province of your empire and mint to make 100 warships. They're worth the 1-1.5% inflation. Warships shouldn't be used in mediterranean wars with OE or France. They can protect your colonies, they can reinforce Mexico, they can transport troops to India against Mughals, Oe, they can do the same about England, its colonies, etc. If Spain lost the seas, you'd be ganged.
-I usually try having land 9 asap in order to invade France and Oe early. after this you don't need to invest hard on it. but keep an eye on your enemies, especially England, never let them have a better crt than yours. you can easily invest hard on land or naval technology to gain a decent tech level quickly. BUT you should invest in infra and trade. So if they're having the same crt, don't worry, keep investing in infra/trade. If they're reaching a new crt level, invest in land/naval too, prehevention is important!
-Spain's decadence in 17th century; this is the period you'll defend yourself. try having huge armies/fleets, try investing in better crt levels, this helps to keep foreign powers in peace with you. If a war can't be avoided, use diplomacy with everyone, buy allies, whatever, you name it, but don't behave cocky, this is NOT 16th century!
-Important: giving a gift to some human countries in a war (always when those countries you get along are in danger, not before or after they're at war) is always an investment. for example, If Poland's growing a lot, fund Russia (don't count much on Sweden for this for obvious reasons, they are dangerous at sea, they have nice technology and very good leaders) Don't let Russia fall, Poland would want to expand in Germany after Russia's annexation, bad for Austria --> bad for you of course. fund Persia, fund Austria, fund France's enemies, invest!
hope this helps a little
