Keep it light so you can easily carry everything long distances over cobblestones if needed.
We each bring a rolling suitcase and day pack, and I use a fanny pack (more secure than a purse).
If you do check bags, make sure they don't contain anything you can't do without, in case they are lost or delayed.
Day packs are invaluable for guidebooks, extra clothes, water bottle, snacks, etc.
Allow space for souvenirs, and if you think you might buy an item of clothing there, pack fewer clothes.
Beware theives and pickpockets: keep nothing in pants pockets, keep purse in front, and never take hands off luggage in airports or train stations.

Clothes:
Lightweight, quick-dry clothes
I bring a thin cloth wrap and use it as a blanket/towel/robe as needed.
Quick-dry swim suit
Plastic bag for laundry
String for clothesline and a few clothespins
Sink stopper, powdered laundry soap, small stain remover stick

Outerwear:
If it will be cold anywhere, a scarf, gloves, and hat add a lot of warmth without taking up much space.
Raincoat or small umbrella or both (depending on weather forecast)
Layers (I bring a sweatshirt, light fleece, and raincoat)

Sun visor or hat
Sunglasses 
sunscreen

Shoes:
Comfy walking shoes 
Sandals

Small empty water bottle (for airplane and in daypack when you're walking around all day)
Small snacks for airplane and in case you have trouble finding food you can eat

Electronics (camera, phone, tablet, chargers, etc.)
Music player
Outlet adapter
I download my pictures every night, just in case my camera gets lost or stolen.

Moneybelt with passport, plane ticket, debit card, credit card, driver's license, American dollars, copy of other person's passport, prescriptions
We also put an image of our passports on our website and bring the link.
Remember to tell your bank you'll be traveling.
Credit card pin number (if yours doesn't have a chip)

Kindle
Reading light (headlamp or small flashlight) - many hotels don't have good reading lights, and a small flashlight makes it easier to navigate dark hotel rooms in the middle of the night, or dark cobblestone streets.

Guidebooks and post-it page markers (make it easier to find info when you're out and about). You can get many guidebooks on Kindle from the library.
Small notepad and pens
Phrasebooks or dictionaries (Smart phone apps?)

Trip itinerary
Hotel written confirmations, email addresses, phone numbers

Airplane comfort (travel pillow, lumbar pillow, footrest, eye drops, nasal gel)

A few zip-lock baggies of various sizes (they're handy for all kinds of things)
One disposable knife, fork, spoon each (very handy for picnic breakfasts and lunches), small tupperware container 

"Business" cards for giving your email address to people you meet

Washcloth (offshore hotels don't have them)

Small photo book with pictures of your life (kids, house, Seattle, hobbies, etc.)

Toiletries
(Liquids and gels in quart zip, except small stuff like chapstick or eye drops)
Besides the usual stuff (toothbrush, paste, floss, deodorant, hair brush, etc.) I bring:
(Small size toothpaste lasts 3 weeks)
Travel pack of wet wipes
Cold medicine (I bring separate benadryl, decongestant, and cough suppressant so I can treat individual symptoms as needed)
Tylenol, ibuprofen, or aspirin
Earplugs and eye cover (essential for sleeping if it's noisy or bright, which hotel rooms often are - airlines may provide, but better to bring your own) 
First aid kit: bandaids, moleskin, antibiotic ointment 
Lip balm/chapstick with SPF (bring a spare!)
Small sewing kit with safety pins and buttons
6-10" piece of duct tape folded up (multi-use, including repairs, notes to maids, etc.)
Medications (if not in opaque pill carrier, make sure container is labeled for customs)
Tissue packets (also very handy for bathrooms that don't have toilet paper)
Anti-diarrheal (Pepto Bismol tabs, loperamide)
Small gel hand sanitizer (1 oz. lasts 3 weeks for 2 people)

Things to do before you leave:
Buy some foreign currency to get you started
Hold postal mail (you can do this online)
Itinerary and contact info to neighbors
Turn down house heat (reprogram)
Return library books
Hide valuables (not in bedroom; kitchen is good)
If you still have a landline, change phone answering machine message and put on message only
Cancel/suspend Netflix
Refill prescriptions