Shortcuts can make life easier. The less I need to take my hands off the keyboard to accomplish a task the more efficient it is. Many of these shortcuts have been around since the TI-89.
Also there are a number of shortcut keys that are the same on the TI-Nspire handheld as they are on most other computers. (Okay Mac friends, read Command for Control.) To get a reminder of these, look at the instructions/tip in parentheses to the right when you are in Menu or Doc. See the image.
In addition to
Ctrl N for New Document
Ctrl O for Open a document from My Documents
Ctrl W to Close the document = same as clicking the x in the right corner
Ctrl S for Save,
there are also
Ctrl C for Copy
Ctrl X for Cut (like scissors)
Ctrl V to Paste (think of the V as ready to squish together, or as a large inverted caret to insert/paste at a certain location.)
Ctrl A to select All or everything. To select just some of the text you can press and hold
Shift and use arrows to select what you want.
Ctrl Z to Undo or you can use Ctrl Esc on the handheld.
Ctrl Y to Redo or Shift Esc on the handheld.
On the number pad on my computer keyboard I have a reminder of the same functionality that is nice to use on a List and Spreadsheet pages, a Program Editor, a Calculator App, or to quickly scroll down when you have a lot of documents in My Documents.

Ctrl 7 is Home
Ctrl 1 End
Ctrl 9 Page Up
Ctrl 3 Page Down
Ctrl 4 Groups the current and next page
Ctrl 6 Ungroups the applications on the page. Do you want the Table or Quick Graph on separate pages? Press Ctrl 6.

You may know that you can press Ctrl Menu for right-click on the handheld to get the contextual menu. Well, on a lot of computers there is a similar icon on a key on your keyboard. That could save a lot of taking your fingers off of a keyboard to mouse right-click.
There are some shortcuts that only work on the handheld (or emulator) and not on a computer keyboard.
Shift + for Integrals - the default appearance is definite integrals, but if you leave those blank the TI-Nspire CAS will do the indefinite integral
Shift - (minus) for the Derivative template.
Ctrl Click to grab a point doesn't have a computer keyboard equivalent. On the handheld you can press and hold the click for 0.8 seconds to grab the point you are clicking.
There are a number of other shortcuts on the TI-Nspire handheld that work exactly the same on the computer. Examples include:
Ctrl Enter gives the approximate solution to a calculation
Ctrl ÷ to make it the nice fancy fraction bar, a.k.a. the fraction template.
Ctrl space (that is the key next to Z) to underscore. This is especially useful on the CAS for units and constants, like _c is the speed of light.
With matrices, you know how there is a carriage return at the bottom right of a TI-Nspire handheld? Well, you can use this to add a row to a matrix.
Shift Enter (carriage return on the handheld) inserts a column.
Ctlr backspace or Del on the handheld to Clear.
Ctrl I to Insert a new page
Ctrl B is used in a program to Check Syntax and Store. This explains why ctrl B and I can't be used for bold and iltacs.

Ctrl R, think Run, is helpful for when you are writing a program and you want to check syntax, store and copy the name of the program to a Calculator application so you can press Enter to run the program. Also in a program

Ctrl F for Find, Ctrl H to Find and Replace in case you want to make the same change several places, and

Ctrl G on a Graph page to see the Entry line. Usually Tab works, but when you have a number of sliders or text, just use the Ctrl G to get back down there. Also note. Instead of pressing Enter after you enter a function to be graphed, use the Down Arrow and you are ready to enter the next function.

Ctrl T on a Graph page to see the table or to remove the table.

Ctrl right arrow or left arrow to advance to the next page or previous page.
Ctrl Up arrow to go to the page sorter view while you are using the emulator (not computer view). Ctrl up again takes you to My Documents. Ctrl down takes you back to where you were.
Ctrl K selects the application. Then you can press backspace/del to delete it or copy/paste it somewhere else.
Ctrl R will recalculate the calculations. Especially on a List and Spreadsheet I have seen this used to get new numbers from randomly generated calculations.
On a Notes page or Question application, use
Ctrl M to insert a Math box
Ctrl E for a Chem Equation box
Ctrl Tab actually does something different on a handheld and on the software. On the handheld it toggles you between the applications on one screen. On the software Ctrl Tab toggle you to the next TI-Nspire file you have open.
In certain places, like Settings,
Tab will move you through the fields. Another example is a dialog box.
Shift Tab moves you through the fields in the reverse order. You went one too far? Shift Tab takes you back one. I've enjoyed using this while filling out information websites and ... on my TI-Nspire.
Finally TAB ZONES can be your friend on many applications. These are so useful that they should get their own 'blog entry.' (Anyone want to write that and include pictures for us?) L&S (Lists and Spreadsheet) to jump from the list up to the top row, D&S (Data & Statistics applications) to jump to the x or y-axis variable to change it, DQ (DataQuest) to tab to a different view and press Enter. Or use Tab to tab down to the green start collecting data button on a DQ application so you can use the Enter button instead of navigating with the mouse ... aim and click. My chemistry colleague and I even discovered a pleasant use of the Tab on a notes page that was filled with Chem Boxes. On certain pages, like Notes and Programs (Math Boxes will slow this end-of-line/beginning-of-line tip down), you can use the Tab to get to the end of the line and then down to the end of the next line. Shift Tab does the reverse. Using this in combination with arrows may be a convenient way to get to the end or beginning of a line.
Many of the above are on the hexa-fold paper you get in the packaging when you buy a new TI-Nspire.
The following can be found on found on page 164-165 (pg 170-171 of the pdf) of the reference guide.
and a lot of this is also available on the 'Cheat Sheet' for TI-Nspire For Dummies website.