I've replaced all 4 speakers on a MY2000 Sienna, but I'm pretty sure the MY2001 is very close if not identical.
SAFETY: While the voltages in speaker wires aren't hazardous to you, it's not a bad idea to either disconnect the negative cable from the battery, or pull the radio's fuse while you're working.
CAUTION: Beware that many of the plastic clips and tabs that align and secure the panel to the door are fragile. Some are replaceable (might be able to get clips cheap at local auto store instead of dealer's ransom prices), others are part of the panel itself. If you break one or two, depending on where they are, it's usually not a problem. Also, there are tools available for prying/releasing the clips, but I'm not sure if they'd work with these clips.
TOOLS: Assuming the speakers you're installing are the correct size (6 3/4" for the MY2000) and aren't too deep, you shouldn't have to do any cutting. The shortest "stubby" #2 Philips head screwdriver should be all you need. You may need wire strippers and electrical tape (better: heat-shrink tubing or liquid electrical tape) - more on that shortly.
That said, my suggestion is NOT to attempt to remove the entire panel. If you're somewhat limber, just pry the corner of the panel where the speaker is located. You should be able to do this with your fingertips and some firm tugging. As each clip "releases" you'll hear a fairly loud "pop." After you get the first one undone, take a close look to see how the compression clip works (goes into a hole in the door). Once you get the corner loosened up, pull it away from the door - gently but firmly.
There are 3 or 4 screws that hold the OEM speaker onto a thick plastic ring, and 3 large, shiny (brass?) screws that hold that ring to the door. If you have good access, just remove the 3 or 4 smaller ones.
Once you have the speaker out, take note of the wires and how they connect. To be honest, I can't recall if there's a proprietary one-piece connector on the end or not. If there is, you may need to splice the connectors/wires that came with the new speakers onto the existing speaker wires (after cutting off the proprietary connector, of course). I strongly suggest making sure the new speaker fits properly before cutting anything! If you do need to splice, be sure the connections are well sealed/insulated. Electrical tape tends to undo itself after repeated cold-hot temperature cycles, which is why I favor heat-shrink tubing or liquid electrical tape (available for about $5 at Home Depot, Lowe's, etc.).
Note the polarities, too. Usually, but not always, the wider speaker tab is positive (sometimes the mfr actually labels the speaker terminals). If you get the polarity wrong, nothing will blow up or anything - but sound (especially bass) may be less than optimal. Interesting to note that the OEM speakers are 2 ohm, whereas almost all auto speakers I've ever worked with are 4 ohm. Installing a 4 ohm speaker isn't a problem (ie, it won't overtax the radio/amp), but may play softer than the original speaker at the same volume knob position (don't worry about it).
Connect the speaker wires to the new speaker, position the speaker connections as close to the "six o'clock" position as you can (not critical). If you have some electrical grease (also known as "bulb grease"), you can put some on the completed connections to help prevent corrosion.
Line up the screw holes, reinstall the screws, and TEST before reinstalling the door panel (done by gently but firmly pushing after lining the pins/clips with their respective holes; if you don't line them up, you WILL break them).
See "How do I replace the passenger side mirror on 2000 Toyota Sienna," if you want to remove the door panel completely.
It is easier with the whole door panel removed, here is how to do it:
1.Remove the Phillips screw that holds the door handle trim piece (under the door handle)
2.Remove the Phillips screw at the upper front under the small round trim cap. Pry gently around all sides of the cap, prying a little more each time.
3.Remove the arm rest by forcing it up with a screw driver. Start with the end towards the front of the car. Start prying at the front edge and next to the door panel. The arm rest has two clips (one at front edge and one about three inches back. Once the two clips are loose the arm rest flips towards you which unhooks the back two prongs.
4.Pry off the control panel. This trim piece has a metal clip that you need to press from the front edge. There is a small indent to allow a small screwdriver. Don't use a screw driver! Use a thin putty knife, but a scredriver will work. There is a lip that the knife will catch on and release the trim. The back of the trim has a fixed clip, so unless you release the front clip it ain't gonna budge! Then unplug the attached wires.
5.Now remove the 2 screws that appeared once the arm rest is off. I think that's all the screws. Pry the bottom of the panel away from the door starting at the bottom back corner (you will feel where there is resistance) and the plastic retaining clips will pop loose one after the other.
6.Your panel should now be completely loose on both sides and the bottom, held on only by the top lip (that is supposed to lift off) and the door handle trim
7.The door handle trim is a little tricky but once you know its not that hard. First of all its held it place by two clips. One is directory over the lock switch and one directly under it. Carefully pry underneath the trim in both of these location and twist the screwdriver to pop off the clips. There is still a hook clip nearer the front of the trim so to pull off the trim you have to kind of pop out the two clips while pulling towards the rear of the car since the hook clips slides out towards the rear.
8.Once that is off its just a matter of lifting the whole panel up until it unhooks from the top of the door.