Hi Mike,
I had a GT16 before I got my AxeFx 3 which pushed me to trade up to the GT22. However, I will share some tips.
1). I purchased a couple of Ext Switches from Analog Endeavors for Page Up/Dn and the other pair for IA mode & Tap Tempo. They were killer and have a small footprint and it opened up 4 buttons on the board for blocks.
RJM sells one here. If you have an expression pedal that uses an Ext Sw I suggest you look at ditching the switch and use Auto Engage in the AxeFx Controllers menu instead.
2). I didn't like the stock layout at first but I scrapped so many layouts that I adapted it for a couple reasons. The Bank Buttons pages through the presets which is really handy and no other combo work together like that. Also, I didn't use IA Mode because I had 22 buttons, and I let my AE's go with the GT16. So, I added Page Up/Dn as IA mode buttons under Bank Up/Dn until I get time to build some side pedals of my own. Hold Functions can be set to be "Only visible in IA Mode" which I use a lot.
3). Hold Functions. My bottom row of buttons have the stock Presets/Scenes and Hold Functions in IA mode only so I can access Scenes and >>Hold Fn to jump to a specific page. I have paired up the following Buttons/Hold Fn: IA Mode/Tuner, Presets/Home (Page1), Bank Up / Preset Menu, Bank Dn / Scene Menu (for 7-8, 6-8 on the GT16 without Scene Names though). I even set the Looper block Hold to take me to a custom page for looper controls. You can even create custom buttons using Hold and Steps to create your own menu. Ron is amazing!
4). Ditch the Global buttons. I only use the Bank and Preset Buttons on Page 1 so that would free up a ton of space on a GT16. On Pages 2 & above I have Page Up/Dn with no IA but you could nest blocks under there if you like. Bonus: my first hack of Global Buttons was to copy the Page Button from Page 1 and paste it to each page. Then I edited each page to point to the page I wanted and not necessarily the next page in the sequence. So the Page button would cycle through the first three pages even though I had the Max Page set to 8. You can then add Page Menu to the Hold Fn to access all the pages.
My layout is still a work in progress but I hope this helps. Any item with ">>" is a Hold function which I borrowed from IARESEE. Thx!