preliminaries

First make sure you have at least NVDA version 2013.2 or later. Also make sure you have to latest patch or Smugglers version.

Open the game executeable. You will either be in the main menu or the screen resolution error screen.

Set NVDA to screen review mode by either using nvda page up until you hear the relevant mode for laptop, or NVDA numpda 7 for desktop. Once that is set up, you shouldn't have issues finding the relevant objects. You use the NVDA key in conjunction with the standard navigation keys to view text on screen. NVDA up and down to view lines, left and right arrows to view individual letters, NVDA+Shift+left/right arrow to move by word, home and end to jump to or to the end of a particular line, NVDA+Control+home or end to jump to the beginning or end of the text for the containing object. You use NVDA and enter to select an option, similarly to a mouse clicking on an object.

When you reach the main menu, select game settings then visually impaired mode. then select yes.

Now the game's output will be mostly fully readable.

Object Navigation

Typically the smugglers interface is laid out hierarchically as most GUI applications are. This generally means that you have parent windows with smaller windows contained within them.
typically the screen review approach reads the text, but this doesn't work in instances where windows are overlaid on top of each other, for example the trade screen overlays the main navigation screen.
to get around this, NVDA's object navigation is useable. This allows for the navigation between objects, IE windows and elements within windows.
Nvda abstracts the objects within the current object into list form. to navigate between these objects, use NVDA's move to previous and next object hotkeys. On laptop these are NVDA+shift+RightArrow and NVDA+Shift+LeftArrow to move to the next or previous object respectively. On desktop these are NVDA+Numpad6 and NVDA+Numpad4. To move to a parent window, use NVDA+Shift+UpArrow for laptop and NVDA+Numpad8 for desktop. To access the list of child objects, use NVDA+Shift+DownArrow for laptop and NVDA+Numpad2 for desktop.

A Note on Mouse Usage

For some events, you will need to use the mouse to activate certain options. To do this, use NVDA shift m (on laptop) or NVDA numpad divide on desktop to move the mouse to the current cursor position (text cursor, not nvda object navigation). Then either use NVDA (laptop: [, desktop: numpad divide) to click on it. Pressing rapidly in succession will double/trippleclick. To right click use (laptop: NVDA+], desktop: numpad multiply).

new game

The first screen of the new game dialog is somewhat odd. You have text, but it is formatted in a way that looks visually fine in columns, but with a screenreader is annoying to deal with. This can be mitigated somewhat using object navigation. To pass this select the faction by nvda entering on it's name. Then select continue.

The next screen is name input, just enter your player's name. You can select a portrait if you want, but this isn't really accessible with nlacking vision. Portrait does determine your in game gender, but this doesn't influence gameplay in the least (apart for flavor text).

The third screen shows professions, which is relatively simple. Just select which one you want, view it's details, then hit continue.

Now the game begins

the tutorial

The tutorial is relatively accessible. The text is generally easy to locate. Object navigation can also be used to locate it. It's location varies depending on your current screen.
When a panel overlays the main screen, for example the trade screen, object navigation can be used to locate the tutorial text. Navigate upward to parent objects until you hear the Smugglers 5 trade, then next object to  the Smugglers 5 option. Move to child object a few times and you'll find the tutorial text.

navigation

The navigation screen is relatively simple. It hsows the available locations and objects in the star system, as well as controls for viewing and manipulating your ship.

The top quarter of the screen (I think, that proportion could be off) shows recent news events. Clicking on them will expand them to read the relevant articles. Below the news list, if playing one of the story backgrounds, is an option to view the current information and objective for your background story.

Below that are the available locations you can move to. Doubleclicking or clicking on a location then selecting travel will move to them.
The lowest portion of the screen shows the game options, such as trade or to take missions. The percentage shows your experience to gain a rank.

combat screen

The combat screen isn't particularly complicated. The topmost portion contains the shields of you and the enemy's ship, as well as your action points and the end turn option. Below that are the various combat options.

Navigating to guns then firing repeatedly can be somewhat irritating. One proposed solution:
Shift the mouse to the gun icon, then left click. Select continue, then just left click again. The mouse cursor will remain at the gun icon's position.
Right clicking on an ability will show it's information.

Skills Screen

This refers to the screen at which you can choose a skill to acquire on rank increase. The skills Screen is annoying to use. You can see your skills at the top portion of the screen, and the rest at the bottom portion. It will take a while of reading, but it is possible to use. To select a skill, right click it then choose skill.
The right click screen does show the required skills, however they are interspersed throughout the rest of the screen. An update to this page would be kind of helpful.

The Spaceport Bar and Hiring Crew Members

The spaceport bar is simple. The crew selection screen again shows a few tables.
The first table has 3 columns, entitled minimum crew, maximum crew, and current crew. The numbers below correspond to the column names.
The table below that consists of 5 columns, entitled crewmen, officers, pirates, marines, and for some odd reason another Marines column. The last marines column is in fact the column for battle droids, which is there for informational purposes.
The first row of that table after the column headers list the number of people you have. For example the first number is the number of crewmen you have, etc.
The row after that lists the price to hire each kind of crewperson.
The next row consists of 5 minus signs. Clicking on one of these will fire a crew member for the respective column. The last column allows you to purchase crewpeople.

Trading

This screen consists of a table.
The first column is the good itself, IE robotics. The second column is the price per unit of the item. The third column lists the amount purchaseable at the current planet, and the fourth is the mount currently aboard your ship.
To buy or sell an item, click on the good in question. Towards the bottom of the screen amounts are listed, IE x1, x25, x100. Click on the desired amount, then buy or sell. Buy all and sell all options are also available.

Hopefully this guide has shown you the fundamentals of smugglers 5 usage with NVDA.