My favorite method is a sandbox but starting small and growing the stakes with the "closed-open-closed" method mentioned earlier in the topic: the starting adventure is an event that forces the characters to join forces and save the day, then they have the chance to explore the land at their leisure until they uncover one of the many secret plots I have prepared and are locked there until solving it. I also have always some kind of "threat on the horizon" (the horde invasion, the evil thieves guild, etc.) to return the campaign to the "plot" if the players go too out of their way with the sandbox elements (it happens).
I do like the players to be part of a group rather than a band of strangers reunited by fate, so I always arrange for them to be part of a faction (either working for a guild, or suggesting the players to form a band of independent adventurers working with the Lord of the City/Captain of the Watch as freelance agents), for the same reasons the OP likes the Guild approach (it makes the players form meaningful connections with the NPCs and the game world).
I also like to play with a fixed home base the players keep returning to/are heavily invested in, as I feel it helps me to easily tailor plots towards the players' background stories. That's why I always reward the players with some form of base (a tower, a fort) near the home town, as this gives them a reason to keep returning to the home town regularly.