I imagine you are a backpack kind of guy, David. So Id suggest something like the Osprey Waypoint 65 ($250), a really nicely designed travel pack from one of the very best packmakers out there. The Waypoint has 4,200 cubic inches of space, which should be adequate for a seasoned traveler such as yourself and will still get you past airline carry-on restrictions. Its designed to let you organize your gear easily, and hold it securely. And like all Osprey packs, the Waypoint carries well. It has a larger sibling, the Waypoint 85 ($280), but you might find it runs afoul of some airlines size restrictions.
I also like packs that can be rolled or carried. Eagle Creeks Switchback Max 22" ($300) has that bi-carry capability. It has decent backpack features, but also a pop-out handle and wheels so you can pull the thing. It has more than 4,000 cubic inches in the main pack and a detachable dayback, and the main bag alone is sized to get you on board without having to check anything.
For a pure roll-around, take a look at Patagonias MLC Wheelie ($229), a well-designed wheeled back that perfectly meets carry-on requirements and has lots of organizational capabilities. A nice bag.