Lots of great advice on this thread.
I try to keep things fairly minimal: capsule-ish wardrobe, like 2 pants, 3, tops, 2 sweaters, one dress and a jacket, usually 2 pairs of shoes (tennis plus either sandals or boots or loafers, depending on trip/weather, maybe flip flop type shoes or water shoes or hiking boots f trip calls for them). I bring a lightweight folding raincoat and expandable bag. I always bring a scarf--even in summer (a cotton scarf) but just can add warmth for unexpectedly cold days or the plane, etc. I also travel with my own very small, fully squishable pillow that I will often use in place of hotel pillows. ALso pack a few detergent sheets.
In booking hotels, I ask for quiet rooms.
Never book 3rd party flights, always with airlines.
plane--usually bring a backpack with a small cross body for phone and wallet; carry copies of passports elsewhere but also have digital copies. I pack change of underwear and shirt and, if a beach vacation, a bathing suit on carryon, along with meds (though I rarely check luggage these days). I bring some snacks for the plane, just in case we are sitting on the tarmac for hours. I also bring several pairs of earbuds and a portable battery to charge on the go.
upgrades: I check frequently for upgrade price and find that they are often least expensive around check in. I will ofte nupgrade for transatlantic overnight and any long haul; i will also pay for exit row or premium seats on long day flights. In general, I pay for things that aid our arrival--if we land and we are tired after long flight, I pay for private transportation to meet us and get us to hotel, etc.
if renting a car, learn the rules of the road and esp whether they have traffic cameras, etc (we saw them all the time in italy). also, in general, read a bit about customs and expectations around dining, tipping, etc. learn a few words in the local language.
like others, I keep my travel toiletries packed and stocked, with a mini first aid (tylenol bandaid, immodium etc).
When traveling with the kids, I really try to return on saturday if school starts monday. Also, kids get their own beds, and if possible we have two rooms. Everyone is in a better mood.
I throw out all food before I go and usually have cleaners come when we are gone. I order instacart delivery of basics to arrive once we land but not earlier in case we are delayed.
I live a couple hours from Dulles, so if we are flying out really early, we will do the park and fly at one of the nearby airport hotels. If we dont need a hotel, I reserve close in parking. IF we are leaving someplace late at night and its long haul, I will look for day hotels, day spa passes, or pay for a hotel so that we can spend the morning/mid day doing stuff and then relax and get clean before getting onto flight.
I generally take local public transportation whenever I can, assuming its efficient and safe. You learn more about the place, and its often better than cabs.