I've not really thought much about this until recently, but I've begun to live my life abiding by these rules. These are my rules and they work very nicely for me, please add your own in the comments.
1) Avoid chains.
I put a lot of effort into not staying in chain hotels and not eating in chain restaurants, with the tools available to us it is fairly easy to do to. A chain has to aim for a minimum level of competence, having a hotel where all the rooms follow a template or a coffee shop that always offers the comfort of the same menu is a waste of life IMO.
2) Eat and drink local.
When I go to a bar I always ask for the drink that is made closest. This supports local industry, reduces transport carbon and food/drink is usually better for not travelling. It also starts a conversation with locals.
3) Eat and drink away from the hotel.
I love travelling to new places, do not give into the temptation to go for the easy option. Go explore!
4) Watch live music in small venues (<2000)
I love live music and I've noticed that the stand-out musical experiences for me are in small venues. There are so many brilliant bands out there, you don't have to keep having this experience.
5) Avoid tourists they'll generally ruin your day.
I'll say it and you can shoot me down; Zoos are rubbish! I can't remember ever having a good time at a zoo. I would rather see a Coyote in the wild than a Panda in a zoo. I queued to see the Mona Lisa at the Louvre, it was disappointing, you could instead spend your time looking at this.
6) Surround yourself with dogs.
They make everything OK
This is by a long way the most important thing I've posted. Now you know all my secrets!